Deck 4: Protein Structure and Function

Question 1

Fully folded proteins typically have polar side chains on their surfaces, where electrostatic attractions and hydrogen bonds can form between the polar group on the amino acid and the polar molecules in the solvent.In contrast, some proteins have a polar side chain in their hydrophobic interior.Which of the following would NOT occur to help accommodate an internal, polar side chain?

A)A hydrogen bond forms between two polar side chains.
B)A hydrogen bond forms between a polar side chain and the protein backbone.
C)A hydrogen bond forms between a polar side chain and an aromatic side chain.
D)Hydrogen bonds form between polar side chains and a buried water molecule.

Answer 1

C

Question 2

Which of the following is NOT a feature commonly observed in α helices?

A)left-handedness
B)1 helical turn every 3.6 amino acids
C)cylindrical shape
D)amino acid side chains that point outward

Answer 2

A

Question 3

Complete the sentence with the best option provided below.The secondary structures of a protein are the

A)regular, repeated folds present in a lowest energy conformation.
B)temporary, unstable protein folding conformations.
C)interactions between polar amino acid side chains.
D)chemical modifications of amino acid side chains.

Answer 3

A

Question 4

The three-dimensional coordinates of atoms within a folded protein are determined experimentally.After researchers obtain a protein's structural details, they can use different techniques to highlight particular aspects of the structure.What visual model best displays a protein's secondary structures (α helices and β sheets)?

A)ribbon
B)space-filling
C)backbone
D)wire

Question 5

Coiled-coils are typically found in proteins that require an elongated structural framework.Which of the following proteins do you expect to have a coiled-coil domain?

A)insulin
B)collagen
C)myoglobin
D)porin

Question 6

Molecular chaperones can work by creating an "isolation chamber." What is the purpose of this chamber?

A)The chamber acts as a garbage disposal, degrading improperly folded proteins so that they do not interact with properly folded proteins.
B)This chamber is used to increase the local protein concentration, which will help speed up the folding process.
C)This chamber serves to transport unfolded proteins out of the cell.
D)This chamber serves to protect unfolded proteins from interacting with other proteins in the cytosol, until protein folding is completed.

Question 7

Polypeptides are synthesized from amino acid building blocks.The condensation reaction between the growing polypeptide chain and the next amino acid to be added involves the loss of

A)a water molecule.
B)an amino group.
C)a carbon atom.
D)a carboxylic acid group.

Question 8

β sheets can participate in the formation of amyloid fibers, which are insoluble protein aggregates.What drives the formation of amyloid fibers?

A)denaturation of proteins containing β sheets
B)extension of β sheets into much longer β strands
C)formation of biofilms by infectious bacteria
D)β-sheet stabilization of abnormally folded proteins

Question 9

The variations in the physical characteristics between different proteins are influenced by the overall amino acid compositions, but even more important is the unique amino acid

A)number.
B)sequence.
C)bond.
D)orientation.

Question 10

Some proteins have α helices, some have β sheets, and still others have a combination of both.What makes it possible for proteins to have these common structural elements?

A)specific amino acid sequences
B)side-chain interactions
C)the hydrophobic-core interactions
D)hydrogen bonds along the protein backbone

Question 11

Which of the following is FALSE about molecular chaperones?

A)They assist polypeptide folding by helping the folding process follow the most energetically favorable pathway.
B)They can isolate proteins from other components of the cells until folding is complete.
C)They can interact with unfolded polypeptides in a way that changes the final fold of the protein.
D)They help streamline the protein-folding process by making it a more efficient and reliable process inside the cell.

Question 12

To study how proteins fold, scientists must be able to purify the protein of interest, use solvents to denature the folded protein, and observe the process of refolding at successive time points.What is the effect of the solvents used in the denaturation process?

A)The solvents break all covalent interactions.
B)The solvents break all noncovalent interactions.
C)The solvents break some of the noncovalent interactions, resulting in a misfolded protein.
D)The solvents create a new protein conformation.

Question 13

Protein structures have several different levels of organization.The primary structure of a protein is its amino acid sequence.The secondary and tertiary structures are more complicated.Consider the definitions below and select the one that best fits the term "protein domain."

A)a small cluster of α helices and β sheets
B)the tertiary structure of a substrate-binding pocket
C)a complex of more than one polypeptide chain
D)a protein segment that folds independently

Question 14

Two or three α helices can sometimes wrap around each other to form coiled-coils.The stable wrapping of one helix around another is typically driven by __________ interactions.

A)hydrophilic
B)hydrophobic
C)van der Waals
D)ionic

Question 15

Which of the following statements is TRUE?

A)Peptide bonds are the only covalent bonds that can link together two amino acids in proteins.
B)There is free rotation around all covalent bonds in the polypeptide backbone.
C)Nonpolar amino acids tend to be found in the interior of proteins.
D)The sequence of the atoms in the polypeptide backbone varies between different proteins.

Question 16

Which of the following is NOT a feature commonly observed in β sheets?

A)antiparallel regions
B)coiled-coil patterns
C)extended polypeptide backbone
D)parallel regions

Question 17

Complete the sentence with the best option provided below.The primary structure of a protein is the

A)amino acid composition.
B)amino acid sequence.
C)average size of amino acid side chains.
D)lowest energy conformation.

Question 18

The correct folding of proteins is necessary to maintain healthy cells and tissues.The presence of unfolded proteins are associated with some neurodegenerative disorders as Alzheimer's disease, Huntington's disease, and Creutzfeldt-Jakob disease (the specific faulty protein is different for each disease).What happens to these disease-causing, unfolded proteins?

A)They are degraded.
B)They bind a different target protein.
C)They form structured filaments.
D)They form protein aggregates.

Question 19

One of the key features of living systems is the use of energy to create and maintain order.A good example is found in the folding of newly synthesized proteins.Which activated carrier molecule is used by chaperone proteins to support protein folding?

A)FADH2
B)ATP
C)NADPH
D)NADH

Question 20

Protein folding can be studied using a solution of purified protein and a denaturant (urea), a solvent that interferes with noncovalent interactions.Which of the following is observed after the denaturant is removed from the protein solution?

A)The polypeptide returns to its original conformation.
B)The polypeptide remains denatured.
C)The polypeptide forms solid aggregates and precipitates out of solution.
D)The polypeptide adopts a new, stable conformation.

Question 21

Studies conducted with a lysozyme mutant that contains an Asp→Asn change at position 52 and a Glu→Gln change at position 35 exhibited almost a complete loss in enzymatic activity.What is the most likely explanation for the decrease in enzyme activity in the mutant?

A)increased affinity for substrate
B)absence of negative charges in the active site
C)change in the active-site scaffold
D)larger amino acids in the active site decreases the affinity for substrate

Question 22

Proteins bind selectively to small-molecule targets called ligands.The selection of one ligand out of a mixture of possible ligands depends on the number of weak, noncovalent interactions in the protein's ligand-binding site.Where is the binding site typically located in the protein structure?

A)on the surface of the protein
B)inside a cavity on the protein surface
C)buried in the interior of the protein
D)forms on the surface of the protein in the presence of ligand

Question 23

The process of generating monoclonal antibodies is labor-intensive and expensive.An alternative is to use polyclonal antibodies.A subpopulation of purified polyclonal antibodies that recognize a particular antigen can be isolated by chromatography.Which type of chromatography is used for this purpose?

A)affinity
B)ion-exchange
C)gel-filtration
D)all of these answers are correct

Question 24

Which of the following methods would be the most suitable to assess whether your protein exists as a monomer or in a complex?

A)gel-filtration chromatography
B)gel electrophoresis
C)western blot analysis
D)ion-exchange chromatography

Question 25

In some cases, small molecules are integral to the function of enzymes, and are dubbed "coenzymes." Which of the following is a coenzyme for the enzyme carboxypeptidase?

A)retinal
B)biotin
C)zinc
D)heme

Question 26

Cyclic AMP (cAMP) is a small molecule that associates with its binding site with a high degree of specificity.Which types of noncovalent interactions are the most important for providing the "hand in a glove" binding of cAMP?

A)hydrogen bonds
B)electrostatic interactions
C)van der Waals interactions
D)hydrophobic interactions

Question 27

Globular proteins fold up into compact, spherical structures that have uneven surfaces.They tend to form multi-subunit complexes, which also have a rounded shape.Fibrous proteins, in contrast, span relatively large distances within the cell and in the extracellular space.Which of the proteins below is NOT classified as a fibrous protein?

A)elastase
B)collagen
C)keratin
D)elastin

Question 28

Energy required by the cell is generated in the form of ATP.ATP is hydrolyzed to power many of the cellular processes, increasing the pool of ADP.As the relative amount of ADP molecules increases, they can bind to glycolytic enzymes, which will lead to the production of more ATP.The best way to describe this mechanism of regulation is

A)feedback inhibition.
B)oxidative phosphorylation.
C)allosteric activation.
D)substrate-level phosphorylation.

Question 29

Motor proteins use the energy in ATP to transport organelles, rearrange elements of the cytoskeleton during cell migration, and move chromosomes during cell division.Which of the following mechanisms is sufficient to ensure the unidirectional movement of a motor protein along its substrate?

A)A conformational change is coupled to the release of a phosphate (P_i).
B)The substrate on which the motor moves has a conformational polarity.
C)A conformational change is coupled to the binding of ADP.
D)A conformational change is coupled to ATP hydrolysis.

Question 30

Lysozyme is an enzyme that specifically recognizes bacterial polysaccharides, which renders it an effective antibacterial agent.Into what classification of enzymes does lysozyme fall?

A)isomerase
B)protease
C)nuclease
D)hydrolase

Question 31

The phosphorylation of a protein is typically associated with a change in activity, the assembly of a protein complex, or the triggering of a downstream signaling cascade.The addition of ubiquitin, a small polypeptide, is another type of covalent modification that can affect the protein function.Ubiquitylation often results in

A)membrane association.
B)protein degradation.
C)protein secretion.
D)nuclear translocation.

Question 32

Which of the following globular proteins is used to form filaments as an intermediate step to assembly into hollow tubes?

A)tubulin
B)actin
C)keratin
D)collagen

Question 33

Antibody production is an indispensable part of our immune response, but it is not the only defense our bodies have.Which of the following is observed during an infection that is NOT a result of antibody-antigen interactions?

A)B cell proliferation
B)aggregation of viral particles
C)systemic temperature increase
D)antibody secretion

Question 34

Proteins can assemble to form large complexes that work coordinately, like moving parts inside a single machine.Which of the following steps in modulating the activity of a complex protein machine is LEAST likely to be directly affected by ATP or GTP hydrolysis?

A)translation of protein components
B)conformational change of protein components
C)complex assembly
D)complex disassembly

Question 35

Which of the following statements about allostery is TRUE?

A)Allosteric regulators are often products of other chemical reactions in the same biochemical pathway.
B)Allosteric regulation is always used for negative regulation of enzyme activity.
C)Enzymes are the only types of proteins that are subject to allosteric regulation.
D)Binding of allosteric molecules usually locks an enzyme in its current conformation, such that the enzyme cannot adopt a different conformation.

Question 36

The Ras protein is a GTPase that functions in many growth factor-signaling pathways.In its active form, with GTP bound, it transmits a downstream signal that leads to cell proliferation; in its inactive form, with GDP bound, the signal is not transmitted.Mutations in the gene for Ras are found in many cancers.Of the choices below, which alteration of Ras activity is most likely to contribute to the uncontrolled growth of cancer cells?

A)a change that prevents Ras from being made
B)a change that increases the affinity of Ras for GDP
C)a change that decreases the affinity of Ras for GTP
D)a change that decreases the rate of hydrolysis of GTP by Ras

Question 37

Which of the following statements is TRUE?

A)Disulfide bonds are formed by the cross-linking of methionine residues.
B)Disulfide bonds are formed mainly in proteins that are retained within the cytosol.
C)Disulfide bonds stabilize but do not change a protein's final conformation.
D)Disulfide bonds are more common for intracellular proteins, compared to extracellular proteins.

Question 38

Which of the following methods would be the most suitable to assess the relative purity of a protein in a sample you have prepared?

A)gel-filtration chromatography
B)gel electrophoresis
C)western blot analysis
D)ion-exchange chromatography

Question 39

Which of the following mechanisms best describes the manner in which lysozyme lowers the energy required for its substrate to reach its transition-state conformation?

A)by binding two molecules and orienting them in a way that favors a reaction between them
B)by altering the shape of the substrate to mimic the conformation of the transition state
C)by speeding up the rate at which water molecules collide with the substrate
D)by binding irreversibly to the substrate so that it cannot dissociate

Question 40

The biosynthetic pathway for the two amino acids E and H is shown schematically in Figure 4-33.You are able to show that E inhibits enzyme V, and H inhibits enzyme X.Which biosynthetic product is most likely the inhibitor of enzyme T? Figure 4-33

A)H
B)B
C)C
D)E

Question 41

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
composition irreversible reversible
covalent lowest sequence
denatured noncovalent stable
highest renatured unstable
A newly synthesized protein generally folds up into a __________ conformation.All the information required to determine a protein's conformation is contained in its amino acid __________.On being heated, a protein molecule will become __________ as a result of breakage of __________ bonds.On removal of urea, an unfolded protein can become __________.The final folded conformation adopted by a protein is that of __________ energy.

Question 43

Determining a protein's sequence, site of covalent modification, or entire three-dimensional structure requires the careful analysis of complex data sets.Which of the data sets below would you have to interpret to solve the structure of a protein by using X-ray crystallography?

Question 44

Which of the following methods would be the most suitable to assess levels of expression of your target protein in different cell types?

A)gel-filtration chromatography
B)gel electrophoresis
C)western blot analysis
D)ion-exchange chromatography

Question 45

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
allosteric ligand secondary
domain primary subunit
helix quaternary tertiary
The α helices and β sheets are examples of protein __________ structure.A protein such as hemoglobin, which is composed of more than one protein __________, has __________ structure.A protein's amino acid sequence is known as its __________ structure.A protein __________ is the modular unit from which many larger single-chain proteins are constructed.The three-dimensional conformation of a protein is its __________ structure.

Question 46

The sequences for three different tripeptides are written out below.Indicate whether you expect to find them in the inner core or on the surface of a cytosolic protein, and explain your answer.
A.serine-threonine-tyrosine
B.alanine-glycine-leucine
C.proline-serine-alanine

Question 47

Typical folded proteins have a stability ranging from 7 to 15 kcal/mole at 37°C.Stability is a measure of the equilibrium between the folded (F) and unfolded (U) forms of the protein.For a protein with a stability of 7.1 kcal/mole, calculate the fraction of protein molecules that would be unfolded at equilibrium at 37°C.The equilibrium constant (K_eq) is related to the standard free energy (ΔG°) by the equation K_eq = 10^{−ΔG°/1.42}.
Figure 4-56

Question 49

Which of the following methods used to study proteins is limited to proteins with a molecular mass of 50 kD or less?

A)X-ray crystallography
B)fingerprinting
C)nuclear magnetic resonance
D)mass spectroscopy

Question 51

Knowing that there are 20 different possible amino acids that can be used at each position in a polypeptide, calculate the number of different polypeptides that could theoretically be produced for a protein that is 180 amino acids in length.Do you expect to find all of these possible protein sequences produced in living systems? Explain your answer.

Question 52

You wish to produce a human enzyme, protein A, by introducing its gene into bacteria.The genetically engineered bacteria make large amounts of protein A, but it is in the form of an insoluble aggregate with no enzymatic activity.Which of the following procedures might help you to obtain soluble, enzymatically active protein? Select all options that may be useful.Explain your reasoning.
A.Make the bacteria synthesize protein A in smaller amounts.
B.Dissolve the protein aggregate in urea, then dilute the solution and gradually remove the urea.
C.Treat the insoluble aggregate with a protease.
D.Make the bacteria overproduce chaperone proteins in addition to protein A.
E.Heat the protein aggregate to denature all proteins, then cool the mixture.

Question 53

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
activation energy inhibitors products
active site isomers substrates
free energy ligand transition state
high-energy low-energy
Any substance that will bind to a protein is known as its __________.Enzymes bind their __________ at the __________.The enzyme hexokinase is so specific that it reacts with only one of the two __________ of glucose.Enzymes catalyze a chemical reaction by lowering the __________, because they provide conditions favorable for the formation of a __________ intermediate called the __________.Once the reaction is completed, the enzyme releases the __________ of the reaction.

Question 54

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
affinity billions ligands
antibodies coiled-coils loops
antigens hundreds size-exclusion
β strands ion-exchange
The human immune system produces __________ of different immunoglobulins, also called __________, which enable the immune system to recognize and fight germs by specifically binding one or a few related __________.The hypervariable structural element that forms the ligand-binding site is comprised of several __________.Purified antibodies are useful for a variety of experimental purposes, including protein purification using __________ chromatography.

Question 55

You have produced a monoclonal antibody that binds to the protein actin.To be sure that the antibody does not cross-react with other proteins, you test your antibody in a western blot assay on whole-cell lysates that have been subjected to electrophoresis under nondenaturing conditions (shown in Figure 4-69A) and denaturing conditions (shown in Figure 4-69B).Does the antibody cross-react with other proteins? If so, does this explain the results in the two western blots? If not, how do you explain the difference observed?
Figure 4-69

Question 56

Use your knowledge of amino acid characteristics to order the peptides below according to the net charge contributed by their side chains at physiological pH (~pH₇).Each peptide contains eight amino acids.Use the single-letter amino acid designations to generate your list, placing the most negatively charged peptide on the left and the most positively charged peptide on the right.In addition, for each peptide, list the total number of positive and negative charges.Remember that, at neutral pH, the amino terminus carries a positive charge and the carboxyl terminus carries a negative charge.
A.YGAKKRA
B.ARRKSTRK
C.DERKQNST
D.DDAEIYSA
E.NQSTYEEG

Question 58

For each of the following, indicate whether the individual folded polypeptide chain forms a globular (G) or fibrous (F) protein molecule.
A.keratin
B.lysozyme
C.elastin
D.collagen
E.hemoglobin
F.actin

Question 59

In an attempt to define the protein domains of protein X, you treat it with a protease and use polyacrylamide gel electrophoresis to analyze the peptides produced.In the past, you have used chymotrypsin to perform this experiment, but the stock of this enzyme has been used up.You find a stock of elastase and decide to use it instead of waiting for a new stock of chymotrypsin to arrive.
A.Give two reasons why elastase is a good substitute for chymotrypsin in this assay.
B.Why might proteolysis of the same substrate by chymotrypsin or elastase yield different results?

Question 60

Protein families arise when a protein sequence that generates a stable fold diverges over many generations and acquires new functions.One example of this can be seen in the globin family.Myoglobin is a stable monomeric protein that can help carry oxygen using a heme molecule.Hemoglobin is stable as a tetramer.It also carries oxygen through the use of heme groups, but it is useful over a much more dynamic range of oxygen than myoglobin.The "globin fold" is structurally conserved across these proteins, but the ability to tetramerize arose through genetic drift and natural selection.Provide an explanation for how the globin sequence can change and still produce the same overall fold.Support your explanation by suggesting the location and type of sequence alterations that might have little effect on the overall protein fold, but may favor the formation of a multi-subunit protein.

Question 61

For each polypeptide sequence listed, choose from the options given below to indicate which secondary structure the sequence is most likely to form upon folding.The nonpolar amino acids are italicized.
A.Leu-Gly-Val-Leu-Ser-Leu-Phe-Ser-Gly-Leu-Met-Trp-Phe-Phe-Trp-Ile
B.Leu-Leu-Gln-Ser-Ile-Ala-Ser-Val-Leu-Gln-Ser-Leu-Leu-Cys-Ala-Ile
C.Thr-Leu-Asn-Ile-Ser-Phe-Gln-Met-Glu-Leu-Asp-Val-Ser-Ile-Arg-Trp
amphipathic α helix hydrophilic β sheet
amphipathic β sheet hydrophobic α helix
hydrophilic α helix

Question 62

Protein Y is a globular protein that normally assembles as a tetramer.You are examining the interactions between the subunits by changing the amino acids on the surface of the protein.You compare the wild-type (nonmutated) protein and a mutant version with a single amino acid substitution.When washed through the same gel-filtration column, mutant protein Y runs through the column more slowly than the normal protein.Which of the following changes in the mutant protein is most likely to explain this result? Explain your choice.
A.the loss of a binding site on the mutant-protein surface through which protein Y normally forms dimers
B.a change that results in the mutant protein acquiring an overall positive instead of a negative charge
C.a change that results in the mutant protein being larger than the wild-type protein
D.a change that results in the mutant protein having a slightly different shape from the wild-type protein

Question 63

Drawn below are segments of β sheets, which are rigid pleated structures held together by hydrogen bonds between the peptide backbones of adjacent strands (Figure 4-79).The amino acid side chains attached to the α-carbons are omitted for clarity.
Figure 4-79
A.For panel (A) and for panel (B), indicate whether the structure is parallel or antiparallel.
B.Draw the hydrogen bonds as dashed lines (||||||).

Question 64

Using the example of the p53 protein, postulate how different combinations of covalent modifications can lead to a wide variety of protein functions.

Question 65

Fill in the blanks with the labels in the list below to identify various parts of the antibody structure in Figure 4-80.
A.constant domain of the light chain
B.constant domain of the heavy chain
C.antigen-binding site
D.variable domain of the heavy chain
E.variable domain of the light chain
Figure 4-80

Question 66

One way in which an enzyme can lower the activation energy required for a reaction is to bind the substrate(s) and distort its structure so that the substrate more closely resembles the transition state of the reaction.This mechanism will be facilitated if the shape and chemical properties of the enzyme's active site are more complementary to the transition state than to the undistorted substrate; in other words, if the enzyme were to have a higher affinity for the transition state than for the substrate.Knowing this, your friend looked in an organic chemistry textbook to identify a stable chemical that closely resembles the transition state of a reaction that converts X into Y.She generated an antibody against this transition-state analog and mixed the antibody with chemical X.What do you think might happen?

Question 67

Some of the enzymes that oxidize sugars to yield usable cellular energy (for example, ATP) are regulated by phosphorylation.For these enzymes, would you expect the inactive form to be the phosphorylated form or the dephosphorylated form? Explain your answer.

Question 68

Enzymes generally make good drug targets because a specific reaction of interest can be targeted with a high degree of selectivity.Consider the following three drugs and explain why, although reaction-specific, the first two produce side effects, while the third does not.
A.Statins inhibit HMG CoA reductase to block intracellular cholesterol synthesis.
B.Methotrexate inhibits dihydrofolate reductase, which subsequently leads to blocked DNA replication.
C.Gleevec® inhibits BCR, a kinase that is only produced in certain types of leukemia cells.

Question 69

Figure 4-78 shows a fatty-acid-binding protein from two different angles.Apart from its two short α helices, its structural elements are extended strands that form a curved β sheet, which is called a β barrel.
A.Draw arrows on the six top strands in panel (A) (those running horizontally) to determine whether the β barrel is made up of parallel or antiparallel strands.
B.Look at panel (B) and predict the relative distribution of polar and nonpolar side chains (inside the barrel or outside the barrel) and explain your answer.
Figure 4-78

Question 70

The protein structure in Figure 4-76 contains four α helices arranged in a bundle.Label each helix by number (1 to 4) starting from the N-terminus and going to the C-terminus, both of which are labeled.List the six possible pairings of these helices, and indicate within each pair whether the helices are parallel or antiparallel.
Figure 4-76

Question 71

Fill in the blank spaces in the table below.The first row has been completed for you.
Table 4-75A