Ch 6: Protein Structure

How do detergents denature proteins?

they bind to hydrophobic regions of the protein preventing those weak interactions

The hydrophobic effect is the main determinant of protein stability and a protein folding into native 3D (tertiary) structure, T/F?

true

Which of the following is not a disease that is caused by protein misfolding? A. Down's syndrome. B. Alzheimer's disease. C. Creutzfeldt-Jakob disease. D. Bovine spongiform encephalopathy.

A. Down's syndrome.

Which treatment is least likely to cause a protein to denature? A. High concentrations of salts. B. Temperatures approaching 100oC. C. High concentrations of detergents like SDS. D. Extremes of pH. E. High concentrations of chaotropic agents like urea or the guanidinium ion.

A. High concentrations of salts.

Which pairs of amino acid side chains could interact in the interior of a protein only via van der Waals interactions? A. Arg, Thr. B. Val, Leu. C. Ser, Ser. D. Gln, His.

B. Val, Leu ; because they're aliphatic

Which statement about disulfide bonds is false? A. Disulfide bonds can occur between two different polypeptide chains. B. Disulfide bonds can occur within a polypeptide chain. C. Disulfide bonds can occur between either Cys or Met residues. D. Disulfide bonds are rare in intracellular proteins because the cytoplasm is a reducing environment. E. Can be reductively cleaved by 2-mercaptoethanol. F. Disulfide bonds help stabilize extracellular proteins. G. Disulfide bonds are not essential for stabilizing a folded protein.

C. Disulfide bonds can occur between either Cys or Met residues.

Who is credited with the discovery of the alpha-helix secondary structure of proteins? A. Chou and Fasman. B. Watson and Crick. C. Linus Pauling. D. Robert Corey.

C. Linus Pauling.

Alpha helices are often flanked by residues such as Asn and Gln, whose side chains can fold back to form hydrogen bonds with one of the four terminal residues of the helix, a phenomenon known as helix _________________

Capping

____________________ residues occur mostly on the surfaces of proteins.

Charged polar

Structure Comparisons Reveal Evolutionary Relationships: Most proteins have a related sequence to other proteins, since evolution tends to conserve the sequences of proteins rather than their structures, T/F?

False

_______________ residues occur mostly in the interior of proteins.

Hydrophobic

The protein's _________________ structure dictates its three-dimensional structure.

Primary

distinct unit of polypeptide that has folded

Subunit

Globular proteins—each with a unique tertiary structure—are built from combinations of secondary structural elements. The proportions of alpha-helices and beta-sheets and the order in which they are connected provide an informative way of classifying and analyzing protein structure, T/F?

True

The conformational flexibility of proteins, leading to displacements of atoms up to ˜2 Angstroms, is known as ________________

breathing

To much salt can do what to the protein?

can cause precipitation

All residues in a typical globular protein are found in alpha-helices, beta-sheets, or reverse turns, T/F?

false

How does high temperature denature proteins?

it breaks the weak interactions within the protein

Must all subunits in a oligometric protein be identical?

no

The Amino acid sequence of a polypeptide is also called its ____________

primary structure

The local spatial arrangement of a protein's backbone atoms without regard to the conformations of its substituent side chains is called its _______________________

secondary structure

The entire three-dimensional structure of a single-chain protein, including that of its side chains is called its _________________________

tertiary structure

How many AA are there in one turn of a alpha helix?

3.6

What are the 2 regular secondary structures?

Alpha helix and Beta sheet

Which of the following statements about the peptide bond is FALSE? A. It is a bond that displays resonance. B. Atoms of the peptide bond are located in a single plane. C. It is formed when water is released from the condensation of an amino group and a carboxylic acid. D. It is a phosphodiester bond. E. It exhibits partial double bond character.

D. It is a phosphodiester bond.

Proteins have static conformations, T/F?

False

What will tell the protein how to fold?

linear AA sequence in primary structure

Analysis of x-ray diffraction data yields a(n) ; analysis of 2D NMR data yields a(n) .

1) electron density map 2) table of interatomic distances

In an alpha-helix, which amino acid residue makes a hydrogen bond to the 3rd residue? A. 6th B. 4th C. 7th D. 1st

7th

Which pairs of amino acid side chains could not interact in the interior of a protein by hydrogen bonding? A. Ala, Lys B. Asp, Asn C. Ser, His D. Gln, Thr

A. Ala, Lys because Ala cannot make an h bond

Which of the following statements about alpha-helices and β-sheets is FALSE? A. Both have conformations that require specific angles of rotation around the peptide bond. B. Both are stabilized by hydrogen bonds between groups in the polypeptide backbone. C. Both have R groups that are oriented away from the core of the structure. D. Both may be found in the same polypeptide

A. Both have conformations that require specific angles of rotation around the peptide bond.

Which pair of amino acid side chains could form an ion pair? A. His, Asp B. Lys, Arg C. Glu, Gly D. Asp, Gln

A. His, Asp , His can become pos and Asp can become neg

he short amino acid sequence shown below occurs within the longer amino acid sequence of a large protein. This specific portion of the amino acid sequence adopts an alpha-helical conformation.............Ala-Val-Ala-Val-Ala-Val-Ala-Val-Ala-Val...............When the protein has adopted its tertiary conformation, which of the following hydrogen bonds are most likely to be formed by groups on the amino acid residues in this short segment? A. Hydrogen bonds with other residues in the same alpha-helix. B. Hydrogen bonds with residues in a neighbouring alpha-helix. C. Hydrogen bonds with water molecules at the surface of the protein. D. None, because Ala and Val side chains are unable to form hydrogen bonds.

A. Hydrogen bonds with other residues in the same alpha-helix.

Which one of the following sequences of five amino acids would most likely be located in the interior of a water soluble globular protein? A. Met-Phe-Pro-Ile-Leu B. Val-Ala-Val-Glu-Val C. Glu-Asn-Ser-Thr-Gln D. Tyr-Phe-Glu-Asn-Leu

A. Met-Phe-Pro-Ile-Leu , because they are all nonpolar side chains

Which of the following statements about quaternary structure is FALSE? A. Quaternary structure is defined as the arrangement of polypeptide backbones in proteins with four subunits. B. Quaternary structure is fine-tuned by ion pairs, disulfide bonds, and hydrogen bonds. C. Quaternary structure exists only in proteins containing more than one polypeptide. D. Quaternary structure is stabilized primarily by hydrophobic interactions.

A. Quaternary structure is defined as the arrangement of polypeptide backbones in proteins with four subunits; it doesn't require 4 subunits

Which of the following statements about quaternary structure is TRUE? A. Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure. B. Quaternary structure requires covalent interactions between polypeptide chains. C. Quaternary structure exists in monomeric proteins. D. Quaternary structure is defined as the precise, 3-D arrangement of polypeptide backbones in proteins with more than one subunit.

A. Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure.

Which of the following amino acid residues form hydrogen bonds with Ala residues located in an alpha-helix? A. Residues located within the same alpha-helix. B. Polar residues involved in the stabilization of tertiary structure. C. None, because Ala is unable to form hydrogen bonds. D. Residues in a neighbouring alpha-helix.

A. Residues located within the same alpha-helix.

Which of the following statements about the alpha-helix and β-sheet are TRUE? A. They are both types of secondary structure. B. They are both usually located in the interior of soluble globular proteins. C. They are both stabilized by hydrogen bonds between amino acid side chains. D. The polypeptide backbone is fully extended in both structures. E. Both A and B

A. They are both types of secondary structure. B. They are both usually located in the interior of soluble globular proteins.

Which of the following statements is TRUE regarding the R-groups of amino acid residues in an alpha-helix? A. They are found on the exterior of the helix. B. They form the hydrogen bonds that produce the helix. C. They are found in the interior of the helix. D. They cause the helix to be right handed. E. They alternate between the outside and the inside of the helix.

A. They are found on the exterior of the helix.

What BEST distinguishes irregular secondary structure from regular secondary structure? A. Unlike regular secondary structure, successive residues in irregular secondary structure do not have the same backbone configuration. B. Unlike regular secondary structure, the backbone of irregularsecondary structure does not form any hydrogen bonds. C. Irregular secondary structure is disordered (random) whereas regular secondary structure is ordered. D. In a given protein the conformation of irregular secondary structure is unknown whereas the conformation of regular secondary structure is known.

A. Unlike regular secondary structure, successive residues in irregular secondary structure do not have the same backbone configuration.

The alpha helices of proteins have an average length of how many residues?

About 12, which is about 3 helical turns

Showed that completely denatured enzymes (ribonuclease) could fold spontaneously into its native (tertiary), enzymatically active form with only the primary sequence to guide it

Anfisen Experiment

Neighboring hydrogen-bonded polypeptide chains run in opposite directions

Antiparallel beta sheet

Which of the following series of amino acids is most likely to be buried in the center of a water-soluble globular protein? A. Pro, Gln, His B. Ala, Leu, Phe C. Glu, Asp, Lys D. Gly, Asn, Ser

B. Ala, Leu, Phe , because they are all nonpolar

Which of the following statements is FALSE? A. Both alpha-helices and beta-sheets have R groups that are oriented away from the core of the structure. B. Both alpha-helices and beta-sheets form only from adjacent (sequential) amino acid residues in the polypeptide. C. Both alpha-helices and beta-sheets are stabilized by hydrogen bonds between groups in the polypeptide backbone. D. Both alpha-helices and beta-sheets have conformations that minimize steric strain in the polypeptide backbone.

B. Both alpha-helices and beta-sheets form only from adjacent (sequential) amino acid residues in the polypeptide.

Which of the following statements is true because of the hydrophobic effect? A. Uncharged polar residues S, T, N, Q, and Y are usually found on the surface of proteins, but may also be found in the interior. B. Nonpolar residues V, L, I, M, and F are found in the interior of proteins. C. The interior of proteins is packed very densely. D. Charged polar residues R, H, K, E, and D are usually found on the surfaces of proteins.

B. Nonpolar residues V, L, I, M, and F are found in the interior of proteins.

Which of the following statements about quaternary structure is TRUE? A. Quaternary structure is defined as the 3D structure of proteins with four subunits. B. Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure. C. Quaternary structure requires covalent interactions between polypeptide chains. D. Quaternary structure exists only in proteins containing prosthetic groups.

B. Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure.

Part of the protein that refers to the atoms that participate in peptide bonds, ignoring the side chains of the AA residues

Backbone

What can reduce disulfide bonds to thiol groups?

Beta-mercaptoethanol

What bonds show free rotation around both bonds in a peptide backbone?

C alpha--C and N--C alpha

What best represents the backbone arrangement of 2 peptide bonds?

C alpha--C--N--C alpha--C--N

Which of the following is FALSE with respect to β-sheets? A. β-sheets are stabilized by non-covalent forces. B. Strands in a β-sheet are connected by irregular loops. C. Amino acid side chains protrude from one side of the β-sheet. D. β-sheets may be parallel or anti-parallel.

C. Amino acid side chains protrude from one side of the β-sheet They protrude from both sides of the sheet

Which group of the 3rd residue is used to make its hydrogen bond in the alpha-helix? A. side chain B. N-H C. C=O D. C-H

C. C=O

Which of the following sequences of amino acids is most likely to be at the surface of a water-soluble globular protein? A. Ile-Ser-Met B. Ala-Leu-Phe C. Glu-Asp-Lys D. Gly-Tyr-Val E. Pro-Phe-Thr

C. Glu-Asp-Lys because they are all polar charged side chains

Why does a decrease in pH alter/disrupt the tertiary structure of an enzyme? A. It reduces disulphide bonds. B. It reduces hydrophobic interactions. C. It disrupts ion pairs/salt bridges. D. It deprotonates prosthetic groups. E. It promotes proteolytic cleavage of peptide bonds.

C. It disrupts ion pairs/salt bridges.

Which statement is not a consequence of the hydrophobic effect? A. The entropy of water increases when proteins fold. B. The folding of proteins is generally a favorable process. C. Metal ions can function to stabilize folded proteins. D. Nonpolar side chains are buried in the interior of a protein.

C. Metal ions can function to stabilize folded proteins.

Which one of the following statements about the alpha-helix is FALSE? A. The alpha-helix has a right handed twist. B. Side chains are located on the outside of an alpha-helix. C. The alpha-helix is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains. D. The alpha-helix is a type of regular secondary structure. E. The alpha-helix contains hydrogen bonds between the carbonyl oxygen of one residue and an amide hydrogen that is four residues closer to the carboxy terminus of the helix.

C. The -helix is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains. AA side chains play no role in secondary structure

Compare the alpha-helix with the structure of double-stranded DNA. Which statement is TRUE for both structures? A. Hydrogen bonds are the primary determinant of stability. B. The backbones are on the outside of the helix. C. The helices are right handed. D. The hydrogen bonds are perpendicular to the axis of the helix.

C. The helices are right handed.

Which of the following is NOT a feature of the peptide bond? A. As a result of the peptide bond, only two dihedral angles per residue in a polypeptide chain can vary freely. B. The trans conformation is much more common than cis. C. The peptide bond has 10% double bond character. D. The peptide bond is highly polar. E. Six atoms, including two alpha-carbons are in the plane of each peptide bond.

C. The peptide bond has 10% double bond character.

Which of the following statements about peptide bonds is FALSE? A. The peptide bond is planar. B. Water is released when a peptide bond is formed. C. The peptide bond has restricted rotation around the bond between the carbonyl carbon and C. D. The peptide bond exhibits partial double bond character

C. The peptide bond has restricted rotation around the bond between the carbonyl carbon and C.

Which one of the following statements about the β-sheet is FALSE? A. The side chains in a β-sheet alternate between the two sides of the sheet. B. β-sheets can be parallel or antiparallel. C. The β-sheet is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains. D. The β-sheet is a type of regular secondary structure. E. The β-sheet contains hydrogen bonds between the carbonyl oxygen of one residue and an amide hydrogen of a residue on an adjacent strand.

C. The β-sheet is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains.

Why do Tyr and/or Trp residues tend to destabilize an alpha-helix when they occur next to each other in a protein? A. The R group of neither amino acid can form a hydrogen bond. B. There are possible covalent interactions between the Tyr and/or Trp side chains. C. There is steric hindrance between the bulky Tyr and/or Trp side chains. D. There is electrostatic repulsion between the Tyr and Trp side chains. E. Both amino acids are highly hydrophobic.

C. There is steric hindrance between the bulky Tyr and/or Trp side chains.

Which one of the following statements about peptide bonds is FALSE. Peptide bonds are: A. covalent. B. rigid and planar, with partial double-bond character. C. charged. D. involved in forming the primary structure of proteins. E. amides.

C. charged

How does low pH denature proteins?

Causes protonation of the side chains of ASP, GLU and HIS preventing electrostatic interactions

How can proteins be disrupted?

Change in temp, pH, urea, guanidinium ion, mercaptoethanol, dithiothreitol, detergents, changes in ionic strength

structure of these proteins help other proteins fold accurately

Chaperone Proteins

the spatial arrangement of the atoms of a molecule that is conferred by the prescence of either double bonds, around which there is no freedom of rotation, or chiral centers, which give rise to stereoisomers

Configuration

The spatial arrangement of substituent groups that, without breaking any bonds, are free to assume different positions in space because of the freedom of bond rotation

Conformation

In an alpha-helix, which amino acid makes a hydrogen bond to the 2nd residue? A. 1st. B. 5th. C. 3rd. D. 6th.

D. 6th. ; n+4

Which one of the following sequences of five amino acids would most likely be located on the surface of a soluble globular protein? A. Met-Phe-Pro-Ile-Leu B. Val-Thr-Val-Glu-Val C. Tyr-Phe-Glu-Asn-Leu D. Glu-Asn-Ser-Thr-Gln

D. Glu-Asn-Ser-Thr-Gln because they are all polar side chains

You have been shown the detailed 3-D structure of an unknown protein. The information indicates that the protein's non-polar amino acid side chains are all exposed on the surface, whereas its polar side chains are all "buried" in the interior. What can you conclude about this protein? A. It is likely to be a lipid-linked membrane protein. B. It is likely to be a peripheral membrane protein. C. It is likely to be a soluble cytosolic protein. D. It is likely to be an integral membrane protein.

D. It is likely to be an integral membrane protein.

Why would you be unlikely to see an alpha-helix containing only the following amino acids: Arg, Lys, Met, Phe, Trp, Tyr, Val? A. helices only contain amino acids with non-polar side chains. B. helices require a minimum of 10 different amino acids arranged ramdomly to fold correctly. C. Steric hindrance between the side chains directed inside the helix. D. Steric hindrance between the side chains projected from the side of the helix.

D. Steric hindrance between the side chains projected from the side of the helix.

What ultimately determines the unique three dimensional structure of soluble globular proteins? A. The exact number of disulfide bonds. B. The number of subunits. C. The exact number of H-bonds. D. The sequence of the amino acid residues. E. The prosthetic groups.

D. The sequence of the amino acid residues.

When collagen is heated it (denatures/ dissolves/ renatures) and becomes (gelatin/ alpha keratin/ beta keratin). The intermolecular bonds that remain intact are (ionic salt bridges/ covalent cross-links/ low barrier hydrogen bonds). The intramolecular forces that are destroyed are (van der Waals interactions, hydrophobic effects and hydrogen bonds/ ionic salt bridges, covalent cross-links and hydrogen bonds/ ionic salt bridges, hydrophobic effects and hydrogen bonds) .

Denatures Gelatin covalent cross links van der Waals, hydrophobic effects and H bonds

Regions of specific, coherent patterns of folding or function

Domains

Which statement about the structure of collagen is FALSE? A. Mutations of Type I collagen in which glycine is replaced at the third position by another amino acid result in diseases like osteogenesis imperfecta (brittle bone disease). B. Collagen has the general repeating sequence (Gly-X-Y)n, where X is often Pro and Y is often 4-hydroxyproline (Hyp). C. In the collagen repeating sequence (Gly-X-Y)n, 5-hydroxylysine (Hyl) sometimes appears at the Y position. D. Collagen is formed by three left-handed helices. E. Glycine is essential at every third position in collagen polypeptides, because the third position passes through the center of the triple helix- this location is so crowded that only a Gly side chain can fit there. F. The three helices of collagen form a left-handed superhelix.

F. The three helices of collagen form a left-handed superhelix.

The beta-strands in a beta-hairpin are parallel, T/F?

False

Which of the following stabilizes the folding of a polypeptide backbone into regular secondary structure? A. Electrostatic interactions. B. Hydrogen bonds. C. Hydrophobic interactions. D. Disulphide bridges. E. Covalent bonds.

H bonds

Intrisically disorded polypeptide segments would contain relatively more residues with( small side chains/ hydrophobic residues/ hydrophilic residues) because such structures would be (compact/ extended/ intertwined) and exposed to aqueous solution. In contrast, (hydrophobic groups/ large side-chain groups/ hydrophilic groups) would tend to aggregate with similar substances in the cell.

Hydrophilic residues extended hydrophobic groups

Laboratory techniques for randomly linking together amino acids typically generate an insoluble polypeptide, yet a naturally occuring polypeptide of the same length is usually soluble. The polypeptide synthesized in a living cell has a sequence that has been optimized by natural selection to fold properly, with (hydrophobic/hydrophilic) residues on the inside and (hydrophobic/hydrophilic) residues on the outside. This is in contrast to the synthetic peptide, whose random sequence cannot direct a coherent folding process. Its (hydrophilic /hydrophobic) side chains would aggregate with other (hydrophilic/ hydrophobic) side chains on different molecules resulting in precipitation from solution

Hydrophobic Hydrophilic Hydrophobic Hydrophobic

Collagen's secondary structure is the (right-handed helix/ left-handed helix/ beta pleated sheet) characteristic of its repeating sequence.

Left handed helix

Particularly stable arrangements of elements of secondary structure including the connections between them, which are found in a variety of proteins

Motifs

Is protein folding an essentially random process?

No

Which AA are typically found in the middle of the Beta turn?

PRO and GLY

Hydrogen bonded chains extend in the same direction

Parallel beta sheet

Has a rigid, planar structure as a consequence of resonance interactions that give the peptide bond about 40% double bond character

Peptide group

Many proteins are composed of 2 or more polypeptide chains, loosely referred to as subunits, this structure refers to the spatial arrangement of its subunits

Quaternary Structure

Collagen's quaternary structure is the arrangement of its three chains in a (left-handed double helix/ left-handed triple helix/ right-handed triple helix/ right-handed double helix)

Right handed triple helix

Which level of protein structure is defined as "the hydrogen bonded arrangement of the polypeptide backbone"? A. Secondary B. Quaternary C. Tertiary D. Primary

Secondary

The local spatial arrangement of a polypeptide's backbone atoms without regard to the conformation of its side chains

Secondary structure

Refers to the 3-D structure of an entire polypeptide, including its side chains

Tertiary structure

Which of the following describes the entire three-dimensional structure of a single polypeptide? A. Quaternary structure B. Tertiary structure C. Primary structure D. Secondary structure

Tertiary structure

What is the most important contribution to the stability of a proteins conformation?

The entropy increase from the decrease in ordered water molecules forming a solvent shell around it

What is a possible problem with the use of x-ray crystallography in determining 3-D structures?

The environment is different than what the native molecule is used to and it will have more bond rotation and flexibility; it may not provide a complete or accurate representation of the biomolecule in vivo

In a alpha helix where are the R groups on the AA residues?

They project outward and downward from the helix to avoid steric hinderance with backbone

The alpha helix is a right handed helix, T/F?

True

The core of the alpha helix is tightly packed and its atoms are in van der Waals contact, T/F?

True

The nonpolar residues Val, Leu, Ile, Met, and Phe occur mostly in the interior of a protein, out of contact with the aqueous solvent. The hydrophobic effects that promote this distribution are largely responsible for the three-dimensional structure of native proteins, T/F?

True

The three-dimensional structures of proteins are most commonly determined by X-ray crystallography, or by nmr studies, T/F?

True

How can you disrupt ionic interactions?

add salt to the solution

Which of the following is TRUE for a β-pleated sheet? A. There are hydrogen bonds perpendicular to the direction of the polypeptide chain. B. The polypeptide chains may be hydrogen bonded together in parallel or anti-parallel orientation. C. The polypeptide chain is almost fully extended. D. All of the above

all of the above

Regular secondary structures are often joined by stretches of peptides called reverse turns or _________

beta bends

Primary structure only contains what type of bonds?

covalent bonds

How does urea denature proteins?

disrupting hydrophobic interactions

What factors stabilize the native structure of a protein?

disulfide bonds, H-bonds, hydrophobic interactions, and ionic interactions

Proteins form identical disulfide bonds both in vitro and in vivo, T/F?

false

The sequences of proteins are more likely to be conserved than their structures during evolution, T/F?

false

Where are the AA residues in relation to each other in secondary structure?

generally near each other

What did Pauling and Corey's studies show about peptide bonds?

peptide bonds are essentially planar, with no rotation about the C-N axis

In aqueous solution, protein conformation is determined by 2 major factors. One is the formation of the max number of hydrogen bonds, what is the other?

placement of hydrophobic AA residues within the interior of the protein

Which 2 AA disrupt the formation of the alpha helix and thus typically do not occur?

proline and glycine

The arrangement of protomers in an oligomeric protein is called the _____________

quaternary structure

Removing the salt concentration will do what to the protein?

renature it

Where are the H-bonds in the alpha helix?

roughly parallel to the helix axis

Experiments on denaturation and renaturation after the reduction and reoxidation of the —S—S— bonds in the enzyme ribonuclease (RNase) have shown that:

the primary sequence of RNAase is sufficient to determine its specific secondary and tertiary structure

Determining the precise arrangement of atoms within a large protein is possible only through what?

x-ray diffraction