Which Statement is True About Macromolecules

Which Statement is True About Macromolecules.


This text is divided into five major sections:

Chemistry of the bonds in biological macromolecules
Helicity in macromolecules
Macromolecular folding
Macromolecular interactions


There are three major types of biological macromolecules in mammalian systems.

  1. Carbohydrates
  2. Nucleic acids
  3. Proteins

Often they are treated separately in unlike segments of a course. In fact, the principles governing the organization of three-dimensional construction are common to all of them, so we will consider them together.

We will brainstorm with the monomer units.

  1. monosaccharide — for sugar
  2. nucleotide — for nucleic acids
  3. amino acid — for proteins

We will describe the features of representative monomers, and see how the monomers bring together to form a polymer.

We will then look at the monomers in each major type of macromolecule to run into what specific structural contributions come from each.

The three-dimensional construction of each blazon of macromolecule will then be considered at several levels of organization.

We volition investigate macromolecular interactions and how structural complementarity plays a office in them.

The stories for proteins, monosaccharides and nucleotides are just variations on the same theme. And so y’all’ll need to larn only 1 design, then apply that pattern to the other systems.

Nosotros will conclude this department of the course with a consideration of denaturation and renaturation — the forces involved in loss of a macromolecule’southward native structure (that is, its normal 3-dimensional structure), and how that structure, one time lost, can exist regained.

Permit’s brainstorm.

Biological macromolecules are polar


These macromolecules are polar [polar: having unlike ends] because they are formed by caput to tail condensation of polar monomers. Let’south look at the iii major classes of macromolecules to run into how this works, and let’due south begin with carbohydrates.

Monosaccharides polymerize to yield polysaccharides.

Glucose is a typical monosaccharide. It has 2 important types of functional group: a carbonyl group (an aldehyde in glucose, some other sugars take a ketone grouping instead.) hydroxyl groups on the other carbons. This is what you need to know near glucose, not its detailed construction.

Glucose exists mostly in ring structures. ( 5-OH adds across the carbonyl oxygen double bail.) This is a so-called internal hemiacetal. The ring tin close in either of two ways, giving rise to anomeric forms, -OH down (the alpha-form) and -OH up (the beta-class)

The anomeric carbon (the carbon to which this -OH is attached) differs significantly from the other carbons. (note: it’s easy to choice out because it is the only carbon with TWO oxygens — ring and hydroxyl — attached.)

Free anomeric carbons have the chemical reactivity of carbonyl carbons because they spend role of their time in the open concatenation form. They can reduce alkaline metal solutions of cupric salts. Sugars with free anomeric carbons are therefore called reducing sugars. The rest of the carbohydrate consists of ordinary carbons and ordinary -OH groups. The point is, a monosaccharide tin therefore exist thought of as having polarity, with one cease consisting of the anomeric carbon, and the other terminate consisting of the rest of the molecule.

Monosaccharides tin polymerize by elimination of the elements of h2o

between the anomeric hydroxyl and a hydroxyl of another saccharide. This is chosen a glycosidic bond.

If two anomeric hydroxyl groups react (head to head condensation) the product has no reducing end (no free anomeric carbon). This is the case with sucrose

If the anomeric hydroxyl reacts with a non-anomeric hydroxyl of another sugar, the production has ends with dissimilar backdrop.

  • A reducing end (with a free anomeric carbon).
  • A nonreducing terminate.

This is the case with maltose.

Since most monosaccharides have more than ane hydroxyl, branches are possible, and are common. Branches result in a more compact molecule. If the branch ends are the reactive sites, more branches provide more reactive sites per molecule.

Permit’s now turn to nucleotides and nucleic acids.

Nucleotides polymerize to yield nucleic acids.

Nucleotides consist of three parts.

  1. Phosphate.
  2. Monosaccharide.
    • Ribose (in ribonucleotides)
    • Deoxyribose, which lacks a ii’ -OH (in deoxyribonucleotides)

    The presence or absenteeism of the 2′ -OH has structural significance that will exist discussed later.

  3. A base.

At that place are four dominant bases; here are three of them:

  1. adenine (purine)
  2. cytosine (pyrimidine)
  3. guanine (purine)

The 4th base is (a pyrimidine)

  • uracil (in ribonucleotides) or
  • thymine (in deoxyribonucleotides)

Be aware that uracil and thymine are very similar; they differ but by a methyl grouping.

You need to know which are purines and which are pyrimidines, and whether it is the purines or the pyrimidines that accept one ring. The reasons for knowing these points chronicle to the mode purines and pyrimidines interact in nucleic acids, which nosotros’ll encompass before long.

Nucleotides polymerize by eliminating the elements of water

to course esters between the 5′-phosphate and the 3′ -OH of another nucleotide.

A three’->5′ phosphodiester bail is thereby formed. The product has ends with unlike properties.

  • An end with a free v’ group (likely with phosphate fastened); this is called the 5′ stop.
  • An end with a free three’ group; this is called the 3′ stop.

Allow’s await at the conventions for writing sequences of nucleotides in nucleic acids. Bases are abbreviated by their initials: A, C, G and U or T. U is normally institute only in RNA, and T is normally found just in Dna. So the presence of U vs. T distinguishes betwixt RNA and Deoxyribonucleic acid in a written sequence.

Sequences are written with the 5′ end to the left and the 3′ end to the right unless specifically designated otherwise.

Phosphate groups are normally not shown unless the author wants to draw attention to them. The following representations are all equivalent.

      uracil  adenine  cytosine  guanine     |        |        |        |  P-ribose-P-ribose-P-ribose-P-ribose-OH  5'    3' 5'    3' 5'    iii' 5'    3'  pUpApCpG UACG 3' GCAU 5'

(Note that in the concluding line the sequence is written in reverse order , simply the ends are appropriately designated.)

Branches are possible in RNA merely not in DNA. RNA has a 2′ -OH, at which branching could occur, while Dna does not. Branching is very unusual; it is known to occur only during RNA modification [the “lariat”], but non in any finished RNA species.

Amino acids polymerize to course polypeptides or proteins.

Amino acids contain a carboxylic acid (-COOH) grouping and an amino (-NH2) grouping. The amino groups are ordinarily attached to the carbons which are alpha to the carboxyl carbons, so they are chosen alpha-amino acids.

The naturally occurring amino acids are optically agile, equally they have four unlike groups attached to one carbon, (Glycine is an exception, having two hydrogens) and have the L-configuration.

The R-groups of the amino acids provide a basis for classifying amino acids. There are many ways of classifying amino acids, simply one very useful way is on the basis of how well or poorly the R-group interacts with h2o

  1. The outset course is the hydrophobic R-groups which tin be aliphatic (such as the methyl grouping of alanine) or aromatic (such as the phenyl group of phenylalanine).
  2. The 2nd class is the hydrophilic R-groups which tin contain neutral polar (such every bit the -OH of serine) or ionizable (such as the -COOH of aspartate) functional groups.

Amino acids polymerize by eliminating the elements of h2o

to form an amide between the amino and carboxyl groups. The amide link thereby formed betwixt amino acids is called a peptide bond.

The product has ends with different properties.

  • An finish with a free amino group; this is called the amino final or N-terminal.
  • An end with a free carboxyl grouping; this is called the carboxyl terminal or C-terminal.

Conventions for writing sequences of amino acids.

Abbreviations for the amino acids are usually used; nearly of the three letter abbreviations are self-axiomatic, such every bit gly for glycine, asp for aspartate, etc.

At that place is also a one-alphabetic character abbreviation system; it is becoming more than common. Many of the one-letter of the alphabet abbreviations are straightforward, for example:

Chiliad = glycine
L = leucine
H = histidine

Others crave a little imagination to justify:

F = phenylalanine (“ph” sounds like “F”).
Y = tyrosine (T was used for threonine, so we settle for the second alphabetic character in the proper name).
D = aspartate (D is the fourth letter in the alphabet, and aspartate has four carbons).

Still others are rather difficult to justify:

West = tryptophan (The bottom half of the 2 aromatic rings look sort of similar a “W”).
K = lysine (if yous tin call up of a good ane for this, allow us know!)

Question: What exercise you suppose “Q” represents?

Y’all should be enlightened this is becoming more and more than commonly used, and you should have the mindset of picking it up equally you are exposed to it, rather than resisting.

Sequences are written with the N-terminal to the left and the C-final to the right.

Although R-groups of some amino acids contain amino and carboxyl groups, branched polypeptides or proteins do not occur.

The sequence of monomer units in a macromolecule is chosen the Principal Structure of that macromolecule. Each specific macromolecule has a unique principal structure.

This concludes our consideration of the relationship betwixt the structures of biological polymers and their monomer subunits. Biosynthesis of these macromolecules will be covered in subsequent lectures. Let’s now begin to investigate the three-dimensional shapes of these macromolecules in solution and the forces responsible for these shapes. It turns out that



Biopolymers consisting of regularly repeating units tend to form helices.

The primal reason for this is that the bail angles of the constituent atoms are never 180 degrees, so linear molecules are not probable; rather, a gentle curve should be expected along the length of the macromolecule.

Just what is a helix? A helical structure consists of repeating units that lie on the wall of a cylinder such that the structure is superimposable upon itself if moved along the cylinder centrality.

A helix looks like a spiral or a screw. A zig-zag is a degenerate helix.

Helices can exist right-handed or left handed. The difference betwixt the two is that:

Right-handed helices or screws accelerate (move away) if turned clockwise.

Examples: standard spiral, bolt, jar lid.

Left-handed helices or screws advance (move away) if turned counterclockwise.

Example: some automobile lug nuts.

Helical organization is an case of secondary construction. These helical conformations of macromolecules persist in solution only if they are stabilized. What might carry out this stabilization?

Stable biological helices are usually maintained past hydrogen bonds.

Allow’s now look at

Helices in carbohydrates.

Carbohydrates with long sequences of alpha (1 -> 4) links accept a weak trend to course helices.

Starch (amylose) exemplifies this structure.

The starch helix is not very stable in the absence of other interactions (iodine, which forms a purple circuitous with starch, stabilized the starch helix), and it normally adopts a random gyre conformation in solution.

In contrast, beta (1 -> 4) sequences favor linear structures. Cellulose exemplifies this structure.

Cellulose is a degenerate helix consisting of glucose units in alternate orientation stabilized by intrachain hydrogen bonds. Cellulose chains lying adjacent can form sheets stabilized by interchain hydrogen bonds.

Helices in nucleic acids.

Single chains of nucleic acids tend to from helices stabilized by base stacking.

The purine and pyrimidine bases of the nucleic acids are aromatic rings. These rings tend to stack like pancakes, only slightly offset so equally to follow the helix. The stacks of bases are in turn stabilized by hydrophobic interactions and by van der Waals forces betwixt the pi-clouds of electrons above and below the aromatic rings.

In these helices the bases are oriented inward, toward the helix axis, and the sugar phosphates are oriented outward, away from the helix axis.

Two lengths of nucleic acid chain can form a double helix stabilized by

  • Base stacking
  • Hydrogen bonds.
Purines and pyrimidines tin can form specifically hydrogen bonded base pairs. Let’s look at how these hydrogen bonds form.
Guanine and cytosine can class a base pair that measures 1.08 nm across, and that contains three hydrogen bonds.
Adenine and thymine (or uracil) can form a base pair that measures one.08 nm beyond, and that contains 2 hydrogen bonds.

Base pairs of this size fit perfectly into a double helix.

This is the so-called Watson-Crick base pairing pattern.

Double helices rich in GC pairs are more than stable than those rich in AT (or AU) pairs because GC pairs have more hydrogen bonds

Now, Specific AT (or AU) and GC base pairing can occur just if the lengths of nucleic acid in the double helix consist of complementary sequences of bases. A must e’er exist contrary T (or U). G must always exist reverse C. Hither’due south a sample of two complementary sequences.



Most Deoxyribonucleic acid and some sequences of RNA accept this complementarity, and form the double helix. It is of import to note, though, that the complementary sequences forming a double helix have contrary polarity. The 2 chains run in contrary directions:



This is described every bit an antiparallel organisation. This organization allows the ii chains to fit together ameliorate than if they ran in the aforementioned direction (parallel organisation).

Consequences of complementarity.

In any double helical structure the amount of A equals the amount of T (or U), and the amount of Thou equals the amount of C. — count the A’southward. T’s, G’s and C’south in this or whatsoever arbitrary paired sequence to prove this to yourself.

Because Deoxyribonucleic acid is usually double stranded, while RNA is not, in Deoxyribonucleic acid A=T and Chiliad=C, while in RNA A does not equal U and Yard does not equal C.

Three major types of double helix occur in nucleic acids. These three structures are strikingly and plainly different in appearance. You could meet the difference if it were out of focus, and yous could feel the differences in the nighttime. This is critically of import, because SO CAN AN ENZYME! Such every bit the enzymes that control the expression of genetic data.

DNA ordinarily exists in the class of a B-helix. Its characteristics:

Right-handed and has ten nucleotide residues per turn.
The plane of the bases is most perpendicular to the helix axis.
There is a prominent major groove and pocket-size groove.
The B-helix may be stabilized by bound water that fits perfectly into the pocket-size groove.

Double-stranded RNA and DNA-RNA hybrids (also DNA in low humidity) exist in the form of an A-helix. Its characteristics:

Right-handed and has 11 nucleotide residues per turn.
The airplane of the bases is tilted relative to the helix axis.
The minor groove is larger than in B-DNA.

RNA is incompatible with a B-helix because the ii’ -OH of RNA would be sterically hindered. (There is no 2′ -OH in DNA.) This is a stabilizing factor you should know.

Deoxyribonucleic acid segments consisting of alternating pairs of purine and pyrimidine (PuPy)n
can form a Z-helix. Its characteristics:

Left-handed (this surprised the discoverers) and has 12 residues (6 PuPy dimers) per turn.
Merely one groove.
The phosphate groups lie on a zig-zag line, which gives ascent to the name, Z-Deoxyribonucleic acid.

The link between the deoxyribose and the purine has a dissimilar conformation in Z-Deoxyribonucleic acid equally compared to A-Dna or B-Deoxyribonucleic acid. Z-Deoxyribonucleic acid is stabilized if it contains modified (methylated) cytosine residues. These occur naturally.

The detailed shape of the helix determines the interactions in which information technology can engage. The geometry of the grooves are important in assuasive or preventing admission to the bases. The surface topography of the helix forms attachment sites for diverse enzymes sensitive to the differences among the helix types. Nosotros’ll see some detailed examples of this later.

The DNA triplex (triple helix):

Start by imagining a B-DNA helix. It is possible under certain circumstances to add a 3rd helix plumbing equipment it into the major groove.

A triplex can grade But if 1 strand of the original B-helix is all purines (A and M) [why you need to know purines from pyrimidines] and the corresponding region of the other strand is all pyrimidines. Regions of DNA with these characteristics are found in control regions for genes, and triplex formation PREVENTS EXPRESSION OF THE Cistron.

The triplex is stabilized by H-bonds in the unusual Hoogsteen base-pairing pattern shown in the slide (along with standard Watson-Crick base pairing).

The being of this construction was known for xx years, but no 1 knew what to make of it. Now, recognizing that it occurs naturally in gene control regions, information technology is getting a great deal of attention in the research literature.

Currently artificial oligonucleotide drugs are existence synthesized that course triplexes with specific natural Dna sequences. Other drugs are beingness developed that stabilize naturally occurring or artificial triplexes. These are showing promise every bit antitumor and antibacterial agents, every bit well every bit potential agents to change enzyme action past controlling enzyme synthesis. It’southward too new to be in even the most modernistic text, but yous volition be seeing more and more of this in the near future. Be enlightened of this construction, know where information technology is found in the gene (at control regions) and its effect on factor expression, and that it is the subject of promising clinical investigations.

Helices in proteins.

Properties of the peptide bond dominate the structures of proteins. The first of these properties is that the peptide bond has partial double character. Fractional double grapheme is conferred by the electronegative carbonyl oxygen, which draws the unshared electron pair from the amide hydrogen.

As a result of having double bond grapheme the peptide bond is

  1. planar
  2. not free to rotate
  3. more than stable in the trans configuration than in the cis

These characteristics restrict the iii-dimensional shapes of proteins because they must be accommodated by any stable structure.

The second major property of the peptide bond is that the atoms of the peptide bond tin can form hydrogen bonds.

Now let’s look at some of the structures that suit the restrictions imposed by the peptide bond. The showtime is the alpha-helix. The alpha-helix is a major structural component of proteins.

Stabilizing factors include:
All possible hydrogen bonds between peptide C=O and N-H groups in the backbone are formed. The hydrogen bonds are all intrachain, between different parts of the same concatenation. A lthough a single hydrogen bond is weak, cooperation of many hydrogen bonds can be strongly stabilizing.
Blastoff-helices must take a minimum length to exist stable ( then there will be enough hydrogen bonds).
All peptide bonds are trans and planar. So, if the amino acrid R-groups exercise not repel one another helix formation is favored.
The net electric charge should be zero or low (charges of the same sign repel).
Adjacent R-groups should be small, to avoids steric repulsion.
Destabilizing factors include:
R-groups that repel one some other favor extended conformations instead of the helix. Examples include large cyberspace electric accuse and adjacent bulky R-groups.
Proline is incompatible with the alpha-helix. The ring formed by the R-grouping restricts rotation of a bond that would otherwise exist costless to rotate. The restricted rotation prevents the polypeptide chain from coiling into an alpha-helix. Occurrence of proline necessarily terminates or kinks blastoff-helical regions in proteins.

Occurrence of the blastoff-helix.

A component of typical globular proteins.
A component of some fibrous proteins, similar blastoff-keratin.

Blastoff-keratin has high tensile strength, every bit first observed past Rapunzel. Information technology is found in hair, feathers, horn; the physical strength and elasticity of pilus make information technology useful in ballistas, onagers, etc.

The beta-pleated canvass is a second major structural component of proteins.

The beta-pleated sheet resembles cellulose in that both consist of extended chains — degenerate helices — lying side by side and hydrogen bonded to one another.

The polypeptide chains of a beta-pleated sheet tin be bundled in two means: parallel (running in the same direction) or antiparallel (running in reverse directions). An edge-on view shows the pleats.

Stabilizing factors for the pleated sheet resemble those for the alpha-helix.
All possible hydrogen bonds betwixt peptide C=O and Northward-H groups in the courage are formed. The hydrogen bonds here are all interchain, unlike those of the alpha-helix.
All peptide bonds are trans and planar.
Small R-groups prevent steric destabilization.
Big R-groups destabilize due to crowding.

Sheets can stack one upon the other, with interdigitating R-groups of the amino acids.

Occurrence of the beta-pleated sheet.

A component of lxxx% of all globular proteins.
In some fibrous proteins.

Egg stalks of sure moths.
Some silk fibroins.

Collagen has an unusual construction. Information technology consists of three polypeptide chains in a triple helix. This is the structure:

3 extended helices of a type called polyproline Two helices (considering polyproline can have this form)
hydrogen bonded to i some other (interchain); no intrachain hydrogen bonds form because each helix is too extended, and hydrogen bonds cannot reach from one level of the helix upwards or downwardly to the next level
placed at the corners of a triangle.
The entire associates is twisted into a superhelix.

The stability of the collagen triple helix is due to its unusual amino acrid composition and sequence. One third of the amino acid residues is glycine, and the glycyl residues are evenly spaced: (Gly Ten Y)n, where 10 and Y are other amino acids is the amino acid sequence of collagen. This places a glycyl residue at each position where the chain is in the interior of the triple helix. There would be no room for a beefy R-group in this position (glycine’southward R-group is H). The high glycine content (with its pocket-size R-group) would otherwise let too much conformational freedom and favor a random whorl.

Proline and hydroxyproline together comprise near 1 third of the total amino acid residues, and Gly Pro Hypro is a common sequence. The relative inflexibility of the prolyl and hydroxyprolyl residues stiffens the chains. The high (proline & hydroxyproline) content prevents germination of an alpha-helix.

Collagen occurs in tough, inelastic tissues, similar tendon. The collagen helix is already fully extended. Unlike the alpha-helix, information technology cannot stretch; tendon ought non to stretch nether heavy load.

Collagen is the single about abundant protein in the body; fortunately collagen defects are rare.

The next level of macromolecular arrangement is

Tertiary structure


3rd structure is the three dimensional organization of helical and nonhelical regions of macromolecules. Let’due south look start at the

Third structure of nucleic acids.

And let’s begin with Dna — many naturally occurring Deoxyribonucleic acid molecules are circular double helices. Most circular double-stranded DNA is partly unwound before the ends are sealed to make the circumvolve.

Partial unwinding is called negative superhelicity.
Overwinding before sealing would be called positive superhelicity.

Superhelicity introduces strain into the molecule. (Think of belongings a whorl leap past the two ends and twisting it to unwind it; it takes try to innovate this strain) The strain of superhelicity tin can be relieved by forming a supercoil. The identical phenomenon occurs in retractable telephone headset cords when they get twisted. The twisted round DNA is said to be supercoiled. The supercoil is more meaty. It is poised to exist unwound, a necessary stride in DNA and RNA synthesis.

RNA — about RNA is single stranded, simply contains regions of self-complementarity.

This is exemplified by yeast tRNA. There are four regions in which the strand is complementary to another sequence within itself. These regions are antiparallel, fulfilling the weather condition for stable double helix germination. Ten-ray crystallography shows that the three dimensional structure of tRNA contains the expected double helical regions.

Big RNA molecules have all-encompassing regions of self-complementarity, and are presumed to course circuitous iii-dimensional structures spontaneously.

Tertiary structure in Proteins

The formation of compact, globular structures is governed by the elective amino acid residues. Folding of a polypeptide concatenation is strongly influenced by the solubility of the amino acid R-groups in water.

Hydrophobic R-groups, as in leucine and phenylalanine, normally orient inwardly, away from h2o or polar solutes.

Polar or ionized R-groups, every bit in glutamine or arginine, orient outwardly to contact the aqueous environment.

Some amino acids, such equally glycine, can be accommodated past aqueous or nonaqueous environments.

The rules of solubility and the tendency for secondary structure formation make up one’s mind how the chain spontaneously folds into its final structure.

Forces stabilizing poly peptide tertiary structure.
Hydrophobic interactions — the tendency of nonpolar groups to cluster together to exclude h2o.
Hydrogen bonding, equally part of any secondary structure, as well as other hydrogen bonds.
Ionic interactions — attraction between unlike electric charges of ionized R-groups.
Disulfide bridges between cysteinyl residues. The R-grouping of cysteine is -CH2-SH. -SH (sulfhydryl) groups can oxidize spontaneously to form disulfides (-S-Due south-).

R-CHii-SH + R’-CHii-SH + O2
= R-CH2-Southward-S-CH2-R’ + H2Otwo

(Nether reducing conditions a disulfide bridge can be broken to regenerate the -SH groups.)

The disulfide bridge is a covalent bail. Information technology strongly links regions of the polypeptide chain that could be afar in the chief sequence. Information technology forms after 3rd folding has occurred, so it stabilizes, but does not determine 3rd structure.

Globular proteins are typically organized into one or more meaty patterns called domains.

This concept of domains is important. In general it refers to a region of a protein. Merely it turns out that in looking at protein after protein, certain structural themes repeat themselves, often, but not e’er in proteins that have similar biological functions. This phenomenon of repeating structures is consequent with the notion that the proteins are genetically related, and that they arose from one another or from a mutual ancestor. In looking at the amino acid sequences, sometimes there are obvious homologies, and you could predict that the 3-dimensional structures would be similar. Just sometimes about identical 3-dimensional structures have no sequence similarities at all!

The four-helix packet domain is a common design in globular proteins. Helices lying next can interact favorably if the properties of the contact points are complementary. Hydrophobic amino acids (like leucine) at the contact points and oppositely charged amino acids along the edges will favor interaction. If the helix axes are inclined slightly (xviii degrees), the R-groups volition interdigitate perfectly along 6 turns of the helix. Sets of iv helices yield stable structures with symmetrical, equivalent interactions. Interestingly, four-helix bundles diverge at ane end, providing a cavity in which ions may bind.

All-beta structures comprise domains in many globular proteins. Beta-pleated sheets fold back on themselves to course barrel-like structures. Role of the immunoglobulin molecule exemplifies this. The interiors of beta-barrels serve in some proteins as bounden sites for hydrophobic molecules such equally retinol, a vitamin A derivative. What keeps these proteins from forming infinitely large beta-sheets is not clear.

Now allow’s look at combined blastoff/beta structures. Beta/alpha8
domains are establish in a variety of proteins which take no obvious functional relationship. They consist of a beta-barrel surrounded past a bike of alpha-helices.


Triose phosphate isomerase.
Domain 1 of pyruvate kinase.

Beta-sheet surrounded by alpha-helices too occur. This is a variation on the theme of beta-construction within and alpha-helix outside.


Lactate dehydrogenase domain ane
Phosphoglycerate kinase domain 2

Now that we are familiar with the structures of single chain macromolecules, we are in a position to look at some of the interactions of macromolecules with other macromolecules and with smaller molecules.

Macromolecular Interactions


Macromolecular interactions involving proteins.

Quaternary construction refers to proteins formed by association of polypeptide subunits. Private globular polypeptide subunits may associate to form biologically active oligomers.

    The association is specific.

  1. A limited number of subunits is involved.
    • Oligo = several; mer = torso, or subunit.
    • 2 (dimer) and 4 (tetramer) are near common, but other aggregates occur, such as trimers, pentamers, etc.
  2. The subunits may be identical or they may be different.
  3. Subunit interaction is entirely noncovalent between complementary regions on the subunit surface.
    • Hydrophobic regions can interact.
    • Hydrogen bonding may occur.
    • Electrostatic (ionic) allure may be involved.

If covalent links exist (such as disulfide bridges) and so the structure is not considered quaternary. In proteins with 4th structure the deaggregated subunits alone are generally biologically inactive.

Here are some examples of 4th structure.

  • Hemoglobin is equanimous of iv subunits of two types, blastoff and beta. It is represented as alphaiibeta2.
  • Triose phosphate isomerase is a dimer of identical subunits.

4th construction in proteins is the almost intricate degree of system considered to be a single molecule. College levels of system are multimolecular complexes.

Incorporation of nonprotein components into proteins

The resulting species are called conjugated proteins. If we establish a classification of proteins past composition we can identify two categories.

  1. Unproblematic proteins consist of polypeptide only.
  2. Conjugated proteins also contain a nonprotein moiety which frequently plays a role in biological role.
    • Information technology may participate in part directly.
    • It may influence the shape of the protein.

Many different kinds of compound are found in conjugated proteins. A few examples are:

Metallic ions

Nomenclature: the word “conjugated” is from the Latin, cum = with and jugum = yoke. The protein and nonprotein moieties are yoked with one another (like oxen) to piece of work together.

The apoprotein = the protein without its nonprotein component.
The prosthetic group = the nonprotein portion lonely.
The conjugated protein = the apoprotein + prosthetic group.


Metals constitute as prosthetic groups of proteins include Mg, Ca, V, Cr, Mn, Fe, Co, Cu, Zn and Mo. (Also W in some archaeobacteria.) These metals can course coordination complexes. They accept electron pairs from atoms with unshared electron pairs. The electron pairs fill up vacant orbitals of the metal ion, such equally sp3d2
orbitals. Some of these metals can hands undergo oxidation-reduction, due east.one thousand.

Fe(II) = Atomic number 26(Three) + e

All are relatively small; no heavy metals (due east.g., Pb, Hg) are included. The roles of metals in proteins are related to these properties.

Roles involving simple binding. include
Complexing several groups of the protein simultaneously, thereby stabilizing the iii-dimensional structure of the protein. The protein acts as a polydentate ligand. Case: thermolysin loses its construction if Ca(II) is removed. [Adv. Enzymol. 56:378]
Binding the protein and another molecule together (east.m., an enzyme and its substrate are ligands of the metallic ion simultaneously).
Participation in the protein’due south part. such as activation of a substrate. When a metallic accepts an electron pair form a jump substrate, the resulting electron deficiency may make the substrate more reactive.
Metals frequently participate in oxidation-reduction. Sometimes bound metals participate directly in biological oxidation-reduction reactions by accepting or altruistic an electron (changing oxidation state).

Sometimes other organic or inorganic compounds share metals with proteins.

Sulfide ions participate in formation of the fe-sulfur centers of redoxins.
Heme — hither the fe is part of a big organic circuitous. Information technology is leap by coordination links to the organic moiety. Binding to the protein is

  1. partly through one of the remaining coordination links.
  2. partly through the organic moiety.


Poly peptide associates with lipid through hydrophobic interactions involving the protein’s hydrophobic R-groups. Lipoproteins are pseudomicellar structures. Micelles are orderly arrays of molecules having polar heads and hydrophobic tails. The arrays are of molecular dimensions (e.g., ii molecules across). In h2o, the polar heads orient outward, and the polar tails cluster in the center of the micelle.

Lipoproteins resemble micelles in some respects. The structure of lipoproteins typically includes the following features. Their outer surface is coated with polar lipids, with poly peptide intermingled. Their interior is a region of randomly oriented neutral lipid.

Lipoproteins are ordinarily much larger than two molecules across. The role of the polar lipid and protein on the surface is to solubilize the neutral lipid interior. Protein interacts with the lipid of lipoproteins through amphipathic helices. Blastoff-helical regions of apolipoproteins have polar amino acids on one surface, and nonpolar ones on the opposite surface. The helix lies on the surface of the structure, with the polar groups oriented outward toward the water, and the nonpolar groups buried in the lipid. (Recall the iv-helix package domains of proteins, in which contacts between helices involved hydrophobic residues at the contact points.)

Consequence of charged surface: (non unlike many proteins) a trend to stick to things.

  1. Lipoprotein concentrations become up in infection. This has a protective effect. (NEJM 6/thirty/92)
    • They bind bacterial endotoxins.
    • They bind and neutralize a wide multifariousness of viruses.
  2. Copper, transferrin and other proteins demark to HDL, making information technology more effective in preventing oxidation of LDL, thereby protecting against atherosclerosis. (PNAS 1992, p. 6993)

Membrane proteins are lipoprotein-like in that they accept nonpolar amino acids in strategic locations to allow interaction with the membrane lipid. Proteins of the membrane surface may be structured like the apoproteins of lipoproteins, with amphipathic helices.

Some membrane proteins transverse the membrane. The region of the protein that is completely immersed in membrane should consist entirely of hydrophobic amino acids. A common structural motif to achieve this is an blastoff-helix consisting of at least 22 hydrophobic amino acyl groups. This makes an alpha-helix long enough to span a membrane. In arrays of membrane-spanning helices, helices in the interior of the array could be shorter.

The trouble of proline in transmembrane “helices:” Generally you find hydrophobic residues in transmembrane helices, and their length is near correct, effectually 24 residues. You also find PROLINE. This is very common. Does it violate the prohibition against proline in the helix? Probably not. The current opinion of qualified protein chemists is that when we eventually determine the verbal structures of these molecules, we volition find the expected kink in the helix at each P residue, and that information technology will bear witness to be important in the biological function of the protein.

Glycoproteins are proteins with saccharide prosthetic groups.

Typical structure — one or more chains of monosaccharide units, 1 to 30 units long. It may be straight or branched, and it is normally covalently linked to the apoprotein in one of three major ways.

  1. It may be N-linked (Blazon I) Due north-acetylglucosamine (a sugar with an acetylated amino grouping in place of a hydroxyl group) at the reducing end of a sugar chain is linked to the amide nitrogen of asparagine remainder. The asparagine residue must be in the sequence, Asn X Thr (or Ser), where 10 is whatever amino acid remainder. This specific sequence is called a sequon. No other asparagine will exercise.
  2. It may be O-linked (Type Ii): Hither the reducing end of a carbohydrate chain (usually N-acetylglucosamine residue) is linked to the hydroxyl of a seryl or threonyl residue.
  3. It may be O-linked (Type 3): In this example The reducing end of a carbohydrate chain (commonly Northward-acetylgalactosamine) is linked to the hydroxyl of a hydroxylysyl balance in collagen. (Hydroxylysine is made from lysine in collagen after the collagen has been synthesized.)

Glycoproteins have two major types of functions.

The first is recognition: carbohydrate prosthetic groups serve as antigenic sites (e.grand., blood grouping substances are carbohydrate prosthetic groups), intracellular sorting signals (mannose 6-phosphate bound to a newly synthesized poly peptide sends it to the lysosomes), etc.

Or they may exist structural components of the organism: E.g., the proteoglycans of cartilage. The central core is a polysaccharide called hyaluronic acid. Many glycoprotein branches are attached to the hyaluronic acid noncovalently. Each branch is a glycoprotein (core protein) with many saccharide chains (chondroitin sulfate — alternate galactosamine and galactose — and keratan sulfate — alternate glucosamine and galactose) fastened covalently (xylose beta-> O-ser). The zipper of the core protein to the hyaluronic acid is mediated by a poly peptide called link protein.

We’ve now seen interactions between protein and metal ions, lipid and carbohydrate. Let’south now plow to

Interactions between proteins and nucleic acids.

We volition encounter that these are based on structural complementarity. In that location are three patterns (motifs) that I want to present.

The zinc finger motif

A small Zn-stabilized structural domain found in proteins that interact with nucleic acids. The zinc finger is a loop of about 25 amino acyl residues stabilized by a Zn cantlet.

Zn complexed to His and/or Cys maintains the structure of the domain.

Dissimilar a -S-S- span, the Zn circuitous will not be broken by reducing atmospheric condition inside the cell.
Dissimilar Cu or Fe, Zn does not participate in oxidation-reduction reactions that could generate free radicals which might impairment nucleic acids.

Other amino acyl residues in the loop are involved in binding to specific nucleotides of the nucleic acid or helping to maintain the folded structure of the domain.

Zinc fingers occur in proteins occur in tandem arrays. They are joined to nearby zinc fingers by brusque linking regions of peptide. They are spaced to fit into the major groove of Deoxyribonucleic acid, with the bases of the alpha-helices downwards in the grooves, and the beta-loops touching the double helix.

The leucine zipper

A pair of amphipathic alpha-helices joining two subunits of a dimeric protein that binds to Deoxyribonucleic acid. Some sites in Dna important to biological control have twofold symmetry: the base of operations sequence is the aforementioned in both directions.

5′ …TGACTCA… 3′
iii’ …ACTGAGT… 5′

A protein designed to bind at such a site might besides exist symmetric; this could be accomplished if the protein were a head-to-head dimer.

A class of Deoxyribonucleic acid bounden proteins appears to grade such dimers through alpha-helices having regularly spaced leucyl residues forth one edge. Interaction between the protein monomer units is idea to be through leucyl residues forth the edges of the amphipathic helices, sort of like the 4-helix package, but with only two helices.

Originally it was idea that the leucyl residues interdigitated (hence the proper noun, “leucine zipper”), but it is at present believed that they face each other (reality in the form of 10-ray crystallography strikes again). In any case, the symmetric dimer binds to the symmetric region of the DNA through special bounden domains.

The helix-turn-helix motif

Two curt adjacent alpha-helices that cantankerous one another. One alpha-helix fits into the major groove of Deoxyribonucleic acid, and interacts with specific bases; this is called the recognition helix. A short segment of protein links the recognition helix to a second helix; this is the turn, and is and then named because information technology contains a then-chosen beta-plow, a well recognized structural chemical element of proteins. The second helix lies across the major groove of DNA, and binds nonspecifically.

A dimeric protein can have a helix-plow-helix motif in each subunit, and if the monomer units are identical information technology can thereby recognize and bind to symmetric DNA structures.



Denaturation is the loss of a poly peptide’s or DNA’due south three dimensional structure. The “normal” 3 dimensional structure is called the native state.

Denaturation is physiological — structures ought not to be as well stable.

  1. Double stranded DNA must come apart to replicate and for RNA synthesis.
  2. Proteins must be degraded nether certain circumstances.
    • To cease their biological action (e.g., enzymes).
    • To release amino acids (e.one thousand., for gluconeogenesis in starvation).

Loss of native structure must involve disruption of factors responsible for its stabilization. These factors are:

  1. Hydrogen bonding
  2. Hydrophobic interaction
  3. Electrostatic interaction
  4. Disulfide bridging (in proteins)

Note that no suspension in the polymer concatenation (disruption of primary construction) is involved in denaturation.

Denaturing agents disrupt stabilizing factors.

  1. Agents that disrupt hydrogen bonding:

    Heat — thermal agitation (vibration, etc.) — volition denature proteins or nucleic acids. Oestrus denaturation of Deoxyribonucleic acid is chosen melting because the transition from native to denatured land occurs over a narrow temperature range. As the purine and pyrimidine bases go unstacked during denaturation they absorb light of 260 nanometers wavelength more strongly. The abnormally low absorption in the stacked state is called the hypochromic effect.

    Urea and guanidinium chloride — work by competition These compounds incorporate functional groups that can accept or donate hydrogen atoms in hydrogen bonding. [movie of structures] At high concentration (8 to ten M for urea, and 6 to 8 M for guanidinium chloride) they compete favorably for the hydrogen bonds of the native construction. Hydrogen bonds of the alpha-helix volition be replaced by hydrogen bonds to urea, for example, and the helix will unwind.

  2. Agents that disrupt hydrophobic interaction.

    Organic solvents, such every bit acetone or ethanol — dissolve nonpolar groups.

    Detergents — dissolve nonpolar groups.

    Cold — increases solubility of nonpolar groups in water. When a hydrophobic group contacts h2o, the water dipoles must solvate information technology by forming an orderly array effectually it. The array is called an “iceberg,” because it is an ordered h2o structure, just not true ice. The ordering of h2o in an “iceberg” decreases the randomness (entropy) of the system, and is energetically unfavorable. If hydrophobic groups cluster together, contact with water is minimized, and less h2o must become ordered. This is the driving strength backside hydrophobic interaction. (The clustering together of hydrophobic groups is also entropically unfavorable, but not as much so as “iceberg” germination.) At low temperatures, solvation of hydrophobic groups past water dipoles is more favorable. The h2o molecules have less thermal energy. They tin “sit still” to form a solvation “iceberg” more easily. The significance of cold denaturation is that cold is not a stabilizing cistron for all proteins. Cold denaturation is important in proteins that are highly dependent on hydrophobic interaction to maintain their native structure.

  3. Agents that disrupt electrostatic interaction.

    pH extremes — About macromolecules are electrically charged. Ionizable groups of the macromolecule contribute to its net accuse (sum of positive and negative charges). Bound ions also contribute to its cyberspace charge. Electric charges of the same sign repel ane some other. If the net charge of a macromolecule is zero or about zippo, electrostatic repulsion will be minimized. The substance will exist minimally soluble, because intermolecular repulsion will be minimal. A compact iii-dimensional structure volition be favored, because repulsion between parts of the same molecule will be minimal. The pH at which the net charge of a molecule is zero is chosen the isoelectric pH (or isoelectric signal).

    pH extremes effect in large net charges on nigh macromolecules. Most macromolecules contain many weakly acidic groups. At low pH all the acidic groups volition exist in the associated state (with a zero or positive charge). So the internet charge on the poly peptide will exist positive. At high pH all the acidic groups will be dissociated (with a nil or negative charge). So the net charge on the protein will be negative. Intramolecular electrostatic repulsion from a big cyberspace charge will favor an extended conformation rather than a compact one.

  4. Agents that disrupt disulfide bridges — destabilize some proteins.

    Agents with free sulfhydryl groups will reduce (and thereby cleave) disulfide bridges.


    2 HO-CH2-CH2-SH + R1-S-S-R2
    = Rane-SH + HS-R2
    + HO-CH2-CHtwo-S-S-CH

Some proteins are stabilized by numerous disulfide bridges; cleaving them renders these proteins more than susceptible to denaturation past other forces.

Renaturation is the regeneration of the native structure of a protein or nucleic acid. Renaturation requires removal of the denaturing atmospheric condition and restoration of conditions favorable to the native structure. This includes

  • Solubilization of the substance if information technology is non already in solution.
  • Adjustment of the temperature.
  • Removal of denaturing agents by dialysis or similar means.
  • In proteins, re-formation of any disulfide bridges.

Usually considerable skill and fine art are required to attain renaturation. The fact that renaturation is feasible demonstrates that the information necessary for forming the right three-dimensional structure of a protein or nucleic acid is encoded in its chief construction, the sequence of monomer units. Merely…

This folding may be tedious; what happens in the cell during protein synthesis? Guidance may be needed for information technology to occur correctly and rapidly.

are intracellular proteins which guide the folding of proteins, preventing wrong molecular interactions. They do Non announced equally components of the final structures. Chaperones are widespread, and chaperone defects are believed to exist the etiology of some diseases. Medical applications of chaperones may be expected to include things such as

  • repair of lacking man chaperones and
  • inhibition of those needed past pathogenic organisms.

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Last modified 1/5/95

Which Statement is True About Macromolecules

Source: https://library.med.utah.edu/NetBiochem/macromol.htm