Chapter 4 The Three-Dimensional Structure of Proteins 1

Chapter 4 The Three-Dimensional Structure of Proteins

Multiple Choice Questions

1. Protein secondary structure

Pages: 120121 Difficulty: 2 Ans: A
In the  helix the hydrogen bonds:

A) are roughly parallel to the axis of the helix.

B) are roughly perpendicular to the axis of the helix.
C) occur mainly between electronegative atoms of the R groups.
D) occur only between some of the amino acids of the helix.
E) occur only near the amino and carboxyl termini of the helix.

2. Protein secondary structure

Page: 120 Difficulty: 2 Ans: B
In an  helix, the R groups on the amino acid residues:

A) alternate between the outside and the inside of the helix.

B) are found on the outside of the helix spiral.
C) cause only right-handed helices to form.
D) generate the hydrogen bonds that form the helix.
E) stack within the interior of the helix.

3. Protein secondary structure

Page: 121 Difficulty: 2 Ans: D
Thr and/or Leu residues tend to disrupt an  helix when they occur next to each other in a protein because:

A) an amino acids like Thr is highly hydrophobic.

B) covalent interactions may occur between the Thr side chains.
C) electrostatic repulsion occurs between the Thr side chains.
D) steric hindrance occurs between the bulky Thr side chains.
E) the R group of Thr can form a hydrogen bond.

4. Protein secondary structure

Page: 122 Difficulty: 1 Ans: D
A D-amino acid would interrupt an  helix made of L-amino acids. Another naturally occurring
hindrance to the formation of an  helix is the presence of:

A) a negatively charged Arg residue.

B) a nonpolar residue near the carboxyl terminus.
C) a positively charged Lys residue.
D) a Pro residue.
E) two Ala residues side by side.

5. Protein secondary structure

Page: 122 Difficulty: 3 Ans: E
An  helix would be destabilized most by:

A) an electric dipole spanning several peptide bonds throughout the  helix.

B) interactions between neighboring Asp and Arg residues.
C) interactions between two adjacent hydrophobic Val residues.
D) the presence of an Arg residue near the carboxyl terminus of the  helix.
2 Chapter 4 The Three-Dimensional Structure of Proteins

E) the presence of two Lys residues near the amino terminus of the  helix.

6. Protein secondary structure

Page: 123 Difficulty: 1 Ans: E
The major reason that antiparallel -stranded protein structures are more stable than parallel
- stranded structures is that the latter:

A) are in a slightly less extended configuration than antiparallel strands.

B) do not have as many disulfide crosslinks between adjacent strands.
C) do not stack in sheets as well as antiparallel strands.
D) have fewer lateral hydrogen bonds than antiparallel strands.
E) have weaker hydrogen bonds laterally between adjacent strands.

7. Protein secondary structure

Page: 124 Difficulty: 1 Ans: C
Amino acid residues commonly found in the middle of  turn are:

A) Ala and Gly.

B) hydrophobic.
C) Pro and Gly.
D) those with ionized R-groups.
E) two Cys.

8. Protein secondary structure

Page: 124 Difficulty: 2 Ans: E
A sequence of amino acids in a certain protein is found to be -Ser-Gly-Pro-Gly-. The sequence is
most probably part of a(n):

A) antiparallel  sheet.
B) parallel  sheet.
C)  helix.
D)  sheet.
E)  turn.

9. Protein tertiary and quaternary structures Page: 125 Difficulty: 1 Ans: B

The three-dimensional conformation of a protein may be strongly influenced by amino acid residues
that are very far apart in sequence. This relationship is in contrast to secondary structure, where the
amino acid residues are:

A) always side by side.

B) generally near each other in sequence.
C) invariably restricted to about 7 of the 20 standard amino acids.
D) often on different polypeptide strands.
E) usually near the polypeptide chain’s amino terminus or carboxyl terminus.

10. Protein tertiary and quaternary structures Page: 127 Difficulty: 3 Ans: D
The -keratin chains indicated by the diagram below have undergone one chemical step. To alter the
shape of the -keratin chains—as in hair waving—what subsequent steps are required?
Chapter 4 The Three-Dimensional Structure of Proteins 3

A) Chemical oxidation and then shape remodeling

B) Chemical reduction and then chemical oxidation
C) Chemical reduction and then shape remodeling
D) Shape remodeling and then chemical oxidation
E) Shape remodeling and then chemical reduction

11. Protein tertiary and quaternary structures Page: 127 Difficulty: 2 Ans: A
Which of the following statements is false?

A) Collagen is a protein in which the polypeptides are mainly in the -helix conformation.
B) Disulfide linkages are important for keratin structure.
C) Gly residues are particularly abundant in collagen.
D) Silk fibroin is a protein in which the polypeptide is almost entirely in the  conformation.
E) -keratin is a protein in which the polypeptides are mainly in the -helix conformation.

12. Protein tertiary and quaternary structures Pages: 133134 Difficulty: 2 Ans: D
Kendrew’s studies of the globular myoglobin structure demonstrated that:

A) “corners” between -helical regions invariably lacked proline residue.

B) highly polar or charged amino acid residues tended to be located interiorally.
C) myoglobin was completely different from hemoglobin, as expected.
D) the structure was very compact, with virtually no internal space available for water.
E) the  helix predicted by Pauling and Corey was not found in myoglobin.

13. Protein tertiary and quaternary structures Pages: 136137 Difficulty: 1 Ans: E
Determining the precise spacing of atoms within a large protein is possible only through the use of:

A) electron microscopy.
B) light microscopy.
C) molecular model building.
D) Ramachandran plots.
E) x-ray diffraction.

14. Protein tertiary and quaternary structures Page: 140 Difficulty: 1 Ans: A
Proteins often have regions that show specific, coherent patterns of folding or function. These
regions are called:

A) domains.
B) oligomers.
C) peptides.
4 Chapter 4 The Three-Dimensional Structure of Proteins

D) sites.
E) subunits.

15. Protein tertiary and quaternary structures Page: 140 Difficulty: 2 Ans: E
Which of the following statements concerning protein domains is true?

A) They are a form of secondary structure.

B) They are examples of structural motifs.
C) They consist of separate polypeptide chains (subunits).
D) They have been found only in prokaryotic proteins.
E) They may retain their correct shape even when separated from the rest of the protein.

16. Protein tertiary and quaternary structures Page: 141 Difficulty: 2 Ans: D
The structural classification of proteins (based on motifs) is based primarily on their:

A) amino acid sequence.

B) evolutionary relationships.
C) function.
D) secondary structure content and arrangement.
E) subunit content and arrangement.

17. Protein tertiary and quaternary structures Page: 141 Difficulty: 1 Ans: C
Proteins are classified within families or superfamilies based on similarities in:

A) evolutionary origin.
B) physico-chemical properties.
C) structure and/or function.
D) subcellular location.
E) subunit structure.

18. Protein tertiary and quaternary structures Page: 144 Difficulty: 1 Ans: B
Which of the following statements about oligomeric proteins is false?

A) A subunit may be similar to other proteins.

B) All subunits must be identical.
C) Many have regulatory roles.
D) Some oligomeric proteins can further associate into large fibers.
E) Some subunits may have nonprotein prosthetic groups.

19. Protein tertiary and quaternary structures Page: 144 Difficulty: 1 Ans: D
A repeating structural unit in a multimeric protein is known as a(n):

A) domain.
B) motif.
C) oligomer.
D) protomer.
E) subunit.

20. Protein tertiary and quaternary structures Page: 144146 Difficulty: 2 Ans: A
Which of the following statements concerning rotational symmetry in proteins is false?

A) It involves rotation of proteins inside the cell.

B) It is frequently seen in the subunits of oligomeric proteins.
C) It is frequently seen in viruses.
D) It may involve rotation about one or more axes.
E) It results in closed, packed structures.
Chapter 4 The Three-Dimensional Structure of Proteins 5

21. Protein denaturation and folding

Page: 147 Difficulty: 2 Ans: C
An average protein will not be denatured by:

A) a detergent such as sodium dodecyl sulfate.

B) heating to 90°C.
C) iodoacetic acid.
D) pH 10.
E) urea.

22. Protein denaturation and folding

Page: 147 Difficulty: 1 Ans: B
Which of the following is least likely to result in protein denaturation?

A) Altering net charge by changing pH

B) Changing the salt concentration
C) Disruption of weak interactions by boiling
D) Exposure to detergents
E) Mixing with organic solvents such as acetone

23. Protein denaturation and folding

Page: 148 Difficulty: 2 Ans: E
Experiments on denaturation and renaturation after the reduction and reoxidation of the —S—S—
bonds in the enzyme ribonuclease (RNase) have shown that:

A) folding of denatured RNase into the native, active conformation, requires the input of energy in
the form of heat.
B) native ribonuclease does not have a unique secondary and tertiary structure.
C) the completely unfolded enzyme, with all —S—S— bonds broken, is still enzymatically active.
D) the enzyme, dissolved in water, is thermodynamically stable relative to the mixture of amino
acids whose residues are contained in RNase.
E) the primary sequence of RNase is sufficient to determine its specific secondary and tertiary
structure.

24. Protein denaturation and folding

Pages: 148149 Difficulty: 2 Ans: A
Which of the following statements concerning the process of spontaneous folding of proteins is false?

A) It may be an essentially random process.

B) It may be defective in some human diseases.
C) It may involve a gradually decreasing range of conformational species.
D) It may involve initial formation of a highly compact state.
E) It may involve initial formation of local secondary structure.

25. Protein denaturation and folding

Pages: 151152 Difficulty: 1 Ans: B
Protein S will fold into its native conformation only when protein Q is also present in the solution.
However, protein Q can fold into its native conformation without protein S. Protein Q, therefore,
may function as a for protein S.

A) ligand
B) molecular chaperone
C) protein precursor
D) structural motif
6 Chapter 4 The Three-Dimensional Structure of Proteins

E) supersecondary structural unit

26. Protein denaturation and folding

Pages: 151153 Difficulty: 2 Ans: D
Which of the following is not known to be involved in the process of assisted folding of proteins?

A) Chaperonins
B) Disulfide interchange
C) Heat shock proteins
D) Peptide bond hydrolysis
E) Peptide bond isomerization

Short Answer Questions

27. Protein secondary structure
Page: 123 Difficulty: 2
Why are glycine and proline often found within a  turn?

Ans: A  turn results in a tight 180° reversal in the direction of the polypeptide chain. Glycine is the
smallest and thus most flexible amino acid, and proline can readily assume the cis configuration,
which facilitates a tight turn.

28. Protein tertiary and quaternary structures Pages: 127128 Difficulty: 2

In superhelical proteins, such as collagen, several polypeptide helices are intertwined. What is the
function of this superhelical twisting?

Ans: The superhelical twisting of multiple polypeptide helices makes the overall structure more
compact and increases its overall strength.

29. Protein tertiary and quaternary structures Page: 129 Difficulty: 2

Why is silk fibroin so strong, but at the same time so soft and flexible?

Ans: Unlike collagen and keratin, silk fibroin has no covalent crosslinks between adjacent strands, or
between its stacked sheets, making it very flexible. Fibroin’s unusual tensile strength derives from
the fact that the peptide backbone of antiparallel -strands is fully extended, and that the R-groups in
the stacked pleated sheets interdigitate, preventing any longitudinal sliding of the sheets across one
another.

30. Protein tertiary and quaternary structures Page: 133 Difficulty: 1

What is typically found in the interior of a water-soluble globular protein?

Ans: Hydrophobic amino acid residues cluster away from the surface in globular proteins, so much of
the protein’s interior is a tightly packed combination of hydrocarbon and aromatic ring R groups with
very few water molecules.

31. Protein tertiary and quaternary structures Pages: 136139 Difficulty: 3

How does one determine the three-dimensional structure of a protein? Your answer should be more
than the name of a technique.

Ans: The protein is crystallized, and the crystal structure is determined by x-ray diffraction. The
pattern of diffracted x-rays yields, by Fourier transformation, the three-dimensional distribution of
electron density. By matching electron density with the known sequence of amino acids in the
protein, each region of electron density is identified as a single atom. Sometimes, the three-
dimensional structure of a small protein or peptide can be determined in solution by sophisticated
analysis of the NMR spectrum of the polypeptide. This technique can also reveal dynamic aspects of
Chapter 4 The Three-Dimensional Structure of Proteins 7

protein structure such as conformational changes. Computer analysis of two-dimensional NMR

spectra can be used to generate a picture of the three-dimensional structure of a protein.

32. Protein tertiary and quaternary structures Page: 136-137 Difficulty: 2

Describe a reservation about the use of x-ray crystallography in determining the three-dimensional
structures of biological molecules.

Ans: To obtain an x-ray picture of a biomolecule, the molecule must be purified and crystallized
under laboratory conditions far different from those encountered by the native molecule.
Biomolecules in the cell also have more flexibility and freedom of motion than can be accommodated
in a rigid crystal structure. Therefore, the static picture obtained from an x-ray analysis of a crystal
may not provide a complete or accurate representation of the biomolecule in vivo.

33. Protein tertiary and quaternary structures Pages: 139141 Difficulty: 1

Explain what is meant by motifs in protein structure.

Ans: Motifs are particularly stable arrangements of elements of secondary structure (e.g.,  helix and
 conformation), including the connections between them, which are found in a variety of proteins.

34. Protein tertiary and quaternary structures Page: 140 Difficulty: 2

Draw a  loop, and describe what is found in the interior of the loop.

Ans: Hydrophobic amino acid residues are usually found in the interior of the loop; these help
stabilize the arrangement through hydrophobic interactions. (See Fig. 4-20, p. 140.)

35. Protein tertiary and quaternary structures Page: 144 Difficulty: 1

Describe the quaternary structure of hemoglobin.

Ans: Each protein molecule is composed of two copies each of two different subunits  and . The
two  protomers are arranged with C2 symmetry.

36. Protein tertiary and quaternary structures Pages: 145146 Difficulty: 2

Describe briefly the two major types of symmetry found in oligomeric proteins and give an example
of each.

Ans: 1) Rotational: In rotational symmetry, subunits are superimposable after rotation about one or
more of the axes. Some examples are hemoglobin and thepoliovirus capsid. 2) Helical: In helical
symmetry, subunits are superimposable after a helical rotation. Some examples are actin filaments
and the tobacco mosaic virus capsid.

37. Protein tertiary and quaternary structures Page: 146 Difficulty: 2

What is the rationale for many large proteins containing multiple copies of a polypeptide subunit?

Ans: Each different polypeptide requires a separate gene that must be replicated and transcribed. It is
therefore more efficient to have fewer genes, encoding shorter polypeptides that can be used to
construct many large proteins.

38. Protein denaturation and folding

Page: 148 Difficulty: 2
Explain (succinctly) the theoretical and/or experimental arguments in support of this statement: “The
primary sequence of a protein determines its three-dimensional shape and thus its function.”

Ans: Anfinsen showed that a completely denatured enzyme (ribonuclease) could fold spontaneously
into its native, enzymatically active form with only the primary sequence to guide it.
8 Chapter 4 The Three-Dimensional Structure of Proteins

39. Protein denaturation and folding

Page: 147 Difficulty: 2
Each of the following reagents or conditions will denature a protein. For each, describe in one or two
sentences what the reagent/condition does to destroy native protein structure.

(a) urea
(b) high temperature
(c) detergent
(d) low pH

Ans: (a) Urea acts primarily by disrupting hydrophobic interactions. (b) High temperature provides
thermal energy greater than the strength of the weak interactions (hydrogen bonds, electrostatic
interactions, hydrophobic interactions, and van der Waals forces, breaking these interactions. (c)
Detergents bind to hydrophobic regions of the protein, preventing hydrophobic interactions among
several hydrophobic patches on the native protein. (d) Low pH causes protonation of the side chains
of Asp, Glu, and His, preventing electrostatic interactions.
40. Protein denaturation and folding
Page: 147 Difficulty: 2
How can changes in pH alter the conformation of a protein?

Ans: Changes in pH can influence the extent to which certain amino acid side chains (or the amino
and carboxyl termini) are protonated. The result is a change in net charge on the protein, which can
lead to electrostatic attractions or repulsions between different regions of the protein. The final effect
is a change in the protein’s three-dimensional shape or even complete denaturation.

41. Protein denaturation and folding

Pages: 148149 Difficulty: 2
Once a protein has been denatured, how can it be renatured? If renaturation does not occur, what
might be the explanation?

Ans: Because a protein may be denatured through the disruption of hydrogen bonds and hydrophobic
interactions by salts or organic solvents, removal of those conditions will reestablish the original
aqueous environment, often permitting the protein to fold once again into its native conformation. If
the protein does not renature, it may be because the denaturing treatment removed a required
prosthetic group, or because the normal folding pathway requires the presence of a polypeptide chain
binding protein or molecular chaperone. The normal folding pathway could also be mediated by a
larger polypeptide, which is then cleaved (e.g., insulin). Denatured insulin would not refold easily.

42. Protein denaturation and folding

Pages: 151153 Difficulty: 2
What are two mechanisms by which “chaperone” proteins assist in the correct folding of
polypeptides?

Ans: Chaperones protect unfolded polypeptides from aggregation by binding to hydrophobic regions.
They can also provide a microenvironment that promotes correct folding.