CHAPTER 4 -- Protein Structure

practice problems

Match each level of protein structure with its description

1. primary

2. secondary

3. tertiary

4. quaternary

1. amino acid sequence

2. backbone H-bonding patterns

3. 3D folding via R-group interactions

4. assembly of multiple polypeptides

each level builds on the previous, from sequence to complex assembly

Which type of bond directly links amino acids in the primary structure of proteins?

A. Ionic bonds

B. Hydrogen bonds

C. Disulfide bonds

D. Peptide bonds

D. peptide bonds

Peptide bonds are covalent bonds formed between the carboxyl group of one amino acid and the amino group of another through a condensation reaction

Which type of interaction is most directly responsible for alpha helix formation and stabilization

A. Disulfide bonds

B. Hydrogen bonds between backbone functional groups

C. Ionic bonds between side chains

D. Hydrophobic clustering

B. Hydrogen bonds between backbone functional groups

backbone hydrogen bonding drives alpha helix formation

T/F: Tertiary structure is maintained primarily by hydrogen bonding along the peptide backbone

false

tertiary structure depends on side-chain interactions (ionic, hydrophobic, disulfide, H-bonds).

T/F: The peptide bond allows free rotation around the C-N bond axis

false

The peptide bond has partial double-bond character due to resonance, making it planar and rigid with no rotation allowed.

Which statement correctly distinguishes a domain from a motif

A. Domains and motifs are the same and can be used interchangeably.

B. Domains are independently folding units often linked to function, motifs are smaller structural patterns that cannot fold on their own.

C. Domains are small recurring patterns, motifs are large independently folding units.

D. Motifs are always made of DNA, domains are made of protein.

B. Domains are independently folding units often linked to function, and motifs are smaller structural patterns that cannot fold on their own

Domains are stable, functional modules; motifs are smaller patterns embedded within domains

Which forces help stabilize tertiary protein structure? (select all that apply)

A. Disulfide bonds

B. Van der Wahls interactions

C. Hydrogen bonds

D. Ionic interactions

E. Peptide bonds

A, B, C, and D

Tertiary structure depends on multiple stabilizing forces: hydrogen bonds, ionic interactions, hydrophobic effects/van der Waals, and disulfide bonds. Recognizing this diversity of interactions shows an understanding of how proteins fold into their 3D conformations.

In an α-helix, the C=O group of residue n forms a hydrogen bond with the N-H group of which residue?

A. n+4

B. n+1

C. n+2

D. n+3

A. n+4

The alpha helix has a regular pattern where each C=O forms a hydrogen bond with the N-H groups four residues ahead in the sequence

What is the net charge of Glu-Gly-Asp at pH 1?

1

at low pH, acidic groups are protonated, giving a net +1

what is the net charge of Ala-Glu-Lys at pH 7?

0

at pH 7 acidic and basic groups balance to neutral

what is the net charge of Arg-Cys-Glu-Gly at pH 11

-2

at high pH, basic groups lose protons and acidic groups are deprotonatedt

The Ramachandran diagram plots the allowed phi and psi angles, with alpha helices typically found in the ____ quadrant

bottom left

The Ramachandran plot maps phi and psi backbone angles, with alpha helices occupying the bottom-left quadrant around phi= -60 and psi= -45

beta-mercaptoethanol denatures proteins by reducing ____ bonds between ____ residues, disrupting ____ structure

disulfide / cysteine / tertiary

beta-mercaptoethanol is a reducing agent that breaks disulfide bonds between cysteine residues, disrupting tertiary structure stabilization

T/F: The presence of an ATP-binding fold in both bacterial helicases and mammalian kinases is an example of evolutionary conservation of domains

true

The fold has been conserved and repurposed across organisms as different as E. coli and elephants

Proteins are built from repeating BLANK that fold independently and have specific functions. Smaller recurring patterns within them are called BLANK. Over evolutionary time, BLANK of these modules shows shared ancestry across organisms, while domain BLANK creates new proteins by recombination.

1. domains

2. motifs

3. conservation

4. shuffling

A researcher discovers a new protein that has an SH2 domain and a kinase catalytic domain. What is the most likely functional implication of this arrangement?

A. The protein is a membrane lipid that binds cholesterol.

B. The protein is only capable of forming quaternary structure.

C. The protein is nonfunctional because it contains multiple domains.

D. The protein can bind phosphorylated tyrosines and catalyze phosphorylation reactions.

D. The protein can bind phosphorylated tyrosines and catalyze phosphorylation reactions

This combination suggests the protein can both recognize signaling partners (via SH2) and carry out phosphorylation

Anfinsen’s experiments with ribonuclease A demonstrated that protein folding information is encoded in the BLANK structure, as evidenced by the spontaneous BLANK after removing urea and BLANK

1. primary

2. refolding

3. B-mercaptoethanol

Anfinsen showed that the amino acid sequence (primary structure) contains all information needed for proper folding by demonstrating reversible denaturation

Which statement best explains why protein folding occurs rapidly despite Levinthal’s paradox?

A. Proteins sample all possible conformations simultaneously

B. Random thermal motion accelerates the process

C. Folding follows a directed pathway with cumulative selection

D. Chaperone proteins eliminate all incorrect conformations

C. Folding follows a directed pathway with cumulative selection

Folding is guided by cumulative selection where favorable local interactions are retains, progressively narrowing the conformational search space.

The hydrophobic effect drives protein folding primarily because:

A. Water molecules gain entropy when released from ordering around hydrophobic groups

B. Hydrophobic residues are repelled by water molecules

C. Hydrophobic residues form strong bonds with each other

D. The protein chain loses entropy upon folding

A. Water molecules gain entropy when released from ordering around hydrophobic groups

When hydrophobic residues cluster together, water molecules are freed from ordered cage-like structures, increasing overall system entropy

T/F: Urea primarily denatures proteins by disrupting covalent bonds in the polypeptide backbone

false

Urea disrupts non-covalent interactions (hydrogen bonds, hydrophobic effects, and ionic interactions) at all structural levels but leaves covalent bonds intact

Which treatment would be most effective for renaturing a protein that was denatured by moderate heat alone (no reducing agents)?

A. Adding more heat

B. Adding β-mercaptoethanol

C. Slowly cooling the solution

D. Adding urea

C. Slowly cooling the solution

If only heat was used and disulfide bonds remain intact, slow cooling allows the protein to refold following its encoded folding pathway

A proteins melting temperature (Tm) is 55°C. A mutation replaces a buried leucine with alanine. Which of the following outcomes is most likely, and why?

A. Tm decreases, because the protein core features less hydrophobic interactions.

B. Tm increases, because alanine forms stronger hydrophobic interactions.

C. Tm is unchanged, because leucine and alanine are both nonpolar.

D. Tm decreases, because alanine introduces steric clashes.

A. Tm decreases, because the protein core features less hydrophobic interactions

Smaller alanine reduces hydrophobic stabilization in the protein core, lowering thermal stability

What is the most immediate structural change in prion diseases?

A. DNA binding domain mutation

B. Disulfide bond cleavage

C. α-helix replaced by β-sheet

D. Primary structure

C. alpha-helix replaced by beta-sheet

Misfolding converts alpha-helices into beta-sheets, forming aggregates

In prion diseases, the pathological form (PrP^Sc) differs from the normal form (PrP^c) primarily in:

A. Amino acid composition

B. Tertiary structure

C. Secondary structure

D. Primary structure

C. Secondary structure

Prion diseases involve conversion from alpha-helix-rich PrP^c to beta-sheet-rich PrP^Sc without changing the amino acid sequence

A protein mutation changing a buried hydrophobic residue to a charged residue would most likely

A. Have no effect on protein folding

B. Destabilize the protein's tertiary structure

C. Affect only quaternary structure

D. Stabilize the protein structure

B. Destabilize the protein’s tertiary structure

Introducing a charged residue in the hydrophobic core disrupts the hydrophobic effect and creates unfavorable electrostatic interactions in the nonpolar environment