Chapter Questions
Draw a cis peptide bond and identify the groups that experience steric interference.
How many peptide bonds are shown in the structure drawn in Fig. $6-7 ?$
Why would you be unlikely to see an $\alpha$ helix containing only the following amino acids: Arg, Lys, Met, Phe, Trp, Tyr, Val?
Calculate the length in angstroms of a 100 -residue segment of the $\alpha$ keratin coiled coil.
The digestive tract of the larvae of clothes moths is a strongly reducing environment. Why is this beneficial to the larvae?
Collagen IV, which occurs in basement membranes, contains a sulfilimine bond (colored red in the structure below) that crosslinks two collagen triple helices. Identify the parent amino acid residues that participate in this linkage.
Describe the primary, secondary, tertiary, and quaternary structures of collagen.
Explain why gelatin, which is mostly collagen, is nutritionally inferior to other types of protein.
Globular proteins are typically constructed from several layers of secondary structure, with a hydrophobic core and a hydrophilic surface. Is this true for a fibrous protein such as $\alpha$ keratin?
Is it possible for a native protein to be entirely irregular-that is, without $\alpha$ helices, $\beta$ sheets, or other repetitive secondary structures?
The X-ray crystallographic analysis of a protein often fails to reveal the positions of the first few and/or the last few residues of a polypeptide chain. Explain.
(a) Is Trp or Gln more likely to be on a protein's surface? (b) Is Ser or Val less likely to be in a protein's interior? (c) Is Leu or Ile less likely to be found in a middle of an $\alpha$ helix? (d) Is Cys or Ser more likely to be in a $\beta$ sheet?
Classify the following proteins as $\alpha, \beta,$ or $\alpha / \beta$(a) KcsA K ' channel (Fig. $10-4$ )(b) thioredoxin (Fig. $23-11)$
Classify the following proteins as $\alpha, \beta,$ or $\alpha / \beta$(a) Grb2 (Fig. $13-9$ )(b) plastocyanin (Fig. $19-19$ )
You are performing site-directed mutagenesis to test predictions about which residues are essential for a protein's function. Which of each pair of amino acid substitutions listed below would you expect to disrupt protein structure the most? Explain.(a) Val replaced by Ala or Phe(b) Lys replaced by Asp or Arg(c) Gln replaced by Glu or Asn(d) Pro replaced by His or Gly
Laboratory techniques for randomly linking together amino acids typically generate an insoluble polypeptide, yet a naturally occurring polypeptide of the same length is usually soluble. Explain.
Researchers introduced prions into normal mice and mice that were genetically predisposed to develop a disease resembling Alzheimer's. Explain why the Alzheimer's-prone mice displayed symptoms of the prion disease much sooner than did the normal mice.
The genetically engineered proteins that accumulate in bacterial inclusion bodies (Fig. $5-2$ ) form amyloid structures. Such proteins are often difficult to recover in functional form from the bacteria. Explain.
In some proteins, the side-chain carboxylate carbon of an N-terminal glutamate residue reacts with the free amino group to form a pentagonal lactam, a cyclic structure containing a $\mathrm{C}=\mathrm{O}$ group. Draw the resulting pyroglutamate residue.
Experiments in mice suggest that pyroglutamylation (see Problem 19 ) increases the rate of aggregation of amyloid- $\beta$ protein. Propose an explanation for this observation.
Helices can be described by the notation $n_{m}$, where $n$ is the number of residues per helical turn and $m$ is the number of atoms, including $\mathrm{H}$ in the ring that is closed by the hydrogen bond.(a) What is this notation for the $\alpha$ helix?(b) Is the $3_{10}$ helix steeper or shallower than the $\alpha$ helix?
Hydrophobic residues usually appear at the first and fourth positions in the seven-residue repeats of polypeptides that form coiled coils.(a) Why do polar or charged residues usually appear in the remaining five positions?(b) Why is the sequence Ile-Gin-Glu-Val-Glu-ArgAsp more likely than the sequence Trp-Gln-Glu-Tyr-Glu-Arg-Asp to appear in a coiled coil?
Which of the following polypeptides is most likely to form an $\alpha$ helix?(a) CRAGNRKIVLETY(b) SEDNFGAPKSILW(c) QKASVEMAVRNSG
Which of the peptides in Problem 23 is least likely to form a $\beta$ strand?
Explain why Pro residues can occupy the N-terminal turn of an $\alpha$ helix.
What types of rotational symmetry are possible for a protein with (a) four or (b) six identical subunits?
Bacterial glutamate synthetase consists of 12 identical subunits arranged in two stacked rings of six subunits. How would you describe this protein's symmetry?
Proteins in solution are often denatured if the solution is shaken violently enough to cause foaming. Indicate the mechanism of this process. (Hint: The nonpolar groups of detergents extend into the air at air-water interfaces.)
Given enough time, will all denatured proteins spontaneously renature?
Describe the intra- and intermolecular bonds or interactions that are broken or retained when collagen is heated to produce gelatin.
Under physiological conditions, polylysine assumes a random coil conformation. Under what conditions might it form an $\alpha$ helix?
Would intrinsically disordered polypeptide segments contain relatively more hydrophilic or hydrophobic residues? Explain.
It is often stated that proteins are quite large compared to the molecules they bind. However, what constitutes a large number depends on your point of view. Calculate the ratio of the volume of a hemoglobin molecule $(65 \mathrm{kD})$ to that of the four $\mathrm{O}_{2}$ molecules that it binds and the ratio of the volume of a typical office $(4 \times 4 \times 3 \mathrm{m})$ to that of the typical (70-kg) office worker that occupies it. Assume that the molecular volumes of hemoglobin and $\mathrm{O}_{2}$ are in equal proportions to their molecular masses and that the office worker has a density of $1.0 \mathrm{g} / \mathrm{cm}^{3}$. Compare these ratios. Is this the result you expected?
In prokaryotes, the error rate in protein synthesis may be as high as $5 \times 10^{-4}$ per codon. What fraction of polypeptides containing(a) 500 residues or(b) 2000 residues would you expect to contain at least one amino acid substitution?
The coat protein of tomato bushy stunt virus consists of 180 chemically identical subunits, each of which is composed of -386 amino acid residues. The probability that a wrong amino acid residue will be biosynthetically incorporated in a polypeptide chain is 1 part in 3000 per residue.(a) Calculate the average number of coat protein subunits that would have to be synthesized to produce a perfect viral coat.(b) What would this number be if the viral coat were a single polypeptide chain with the same number of residues that it actually has?
Not all heat shock proteins are chaperones; some are proteins that facilitate the degradation rather than the refolding of other proteins. Explain why the rate of protein degradation would increase during heat shock.
Protein denaturation can be triggered by a variety of environmental insults, including high temperature, covalent modification, and oxidation. Explain why researchers have observed a correlation between the level of heat shock proteins and the ratio of oxidized to reduced glutathione (see Section 4-3B) in cells subjected to oxidative stress.
Explain why $\beta$ sheets are less likely to form than $\alpha$ helices during the earliest stages of protein folding.
The GroEL/ES cycle diagrammed in Fig. $6-45$ circulates only in the clockwise direction. Explain the basis for this irreversibility in terms of the sequence of structural and binding changes in the GroEL/ES system.