Lecture 6

Question 1

State the 3 Non-covalent interactions that govern protein folding stability

Answer 1

Van der Waals interactions (short range repulsion)

Hydrogen Bonds

Electrostatic Forces (ex. ion pairs and salt bridges)

Question 2

Describe Hydrophobic interactions that govern protein folding stability

Answer 2

Nonpolar groups do not interact favorably with water, therefore the bonds they form are primarily due to their exclusion from water

Question 3

The hydrophobic interaction is a major factor in the ____ and stability of hydrophobic interactions in proteins

Answer 3

folding

Question 4

Hydrogen Bonds are much _____ than covalent bonds (has to do with the strength of the bond). Give a reason why this is the case.

Answer 4

Weaker

Hydrogen bonds are 1 A longer than covalent bonds

Question 5

State 3 possible Hydrogen Bonds

Answer 5

N-H

O-H

F-H

Question 6

Name the 4 determinants of folding

Answer 6

Secondary Structure

Hierarchical folding

Hydrophobic Effect

Context dependent

Question 7

Alpha-helix structures are stabilized by intrachain ______ bonds between which groups?

Answer 7

Hydrogen

between NH and C=O groups

Question 8

Compare “right handed” and “left handed” alpha helix structures in terms of clockwise or counter-clockwise. Which of these structures is found in proteins?

Answer 8

Right handed = clock-wise

left handed = counter clock wise

alpha-helices in proteins are right-handed

Question 9

Beta-sheets are stabilized by hydrogen bonding between what?

Answer 9

polypeptide strands

Question 10

Describe what the structure of Beta-sheets are composed of AND what interaction binds them together

Answer 10

Beta-sheets are composed of 2 or more beta strands that are fully extended and are linked together via hydrogen bonds

Question 11

True or False:

Beta sheets can run in either a parallel direction or in an antiparallel direction. explain.

Answer 11

True

Question 12

Give the 3 names that describe the beta-sheet structure’s turn in order to form compact and globular shapes for a polypeptide chain

Answer 12

Reverse turn

Beta-turn

Hairpin turn

Question 13

What are the groups that form hydrogen bonds that provide stability for beta sheet proteins?

Answer 13

C=O and NH groups

Question 14

True or False:

Omega loops only participate in protein-protein interactions. explain.

Answer 14

False

Omega loops participate in both protein-protein interactions AND interactions with other molecules as well

Question 15

State the characteristic structure and type of interactions that form superhelix, Alpha-helical coiled coil. (alpha-keratin)

Answer 15

Characterized by a central region of 300 AA’s that contains Heptad repeats (allows 2 alpha-helices to interact with one another)

The 2 helices that come together to form the superhelix alpha-keratin, associate with one another via weak interactions (Van der Waals forces and Ionic interactions)

Question 16

Describe what is unique about the structure of Bovine insulin (2 things)

Answer 16

the alpha-chain has an intra-chain disulfide bond AND the 2 chains that form the structure of bovine insulin are linked by interchain disulfide bonds

Question 17

Explain the steps that are described by the “folding funnel” that describes the entropy and energy level associated with a folding protein

Answer 17

1. rapid formation of secondary structure
2. formation of domains through cooperative aggregation (“folding nuclei” concept)
3. Formation of assembled domains (“molten globule” concept)
4. Adjustment of Conformation
5. A more rigid structure is formed (finishing touches)

Question 18

In Calmodulin, a Ca2+ sensing molecule, how many repeating motifs are present and why are these useful?

Answer 18

it has 4 repeating motifs and they are useful bc each motif can bind to a Ca2+ ion (it can bind to a maximum of 4 of these ions)

Question 19

Describe the concept of “context-dependent” conformations of a peptide sequence

Answer 19

When the exact same peptide chain can take on alternative conformations, depending on the protein it is currently a part of

ex. VDLLKN exists as an alpha helix in one protein and a beta-strand in another

Question 20

Describe the 2 context-dependent conformations of Lymphotactin and which of these is more prevalent

Answer 20

Lymphotactin can exist as a chemokine structure or as a Glycosaminoglycan-binding structure

(TRICK) These conformations exist in equilibrium

Question 21

Describe the structure of the Molten Globule State

Answer 21

Molten Globule State: an intermediate conformational state between the native and the fully unfolded states of a globular protein

(basically has pants on, but isn’t wearing a belt ; half ready, half chilling)

Question 22

State the 5 specific characteristics of the Molten Globule State of a protein

Answer 22

1. the presence of a “native-like” content of secondary structure
2. The absence of a specific tertiary structure produced by the tight packing of AA side chains
3. Compactness in the overall shape of the protein molecule, with a radius 10-30% larger than that of the native state
4. The presence of a loosely packed hydrophobic core that increases the hydrophobic surface area accessible to the solvent
5. It is not specific and occurs in the early state of protein folding

Question 23

Describe the globule and molten side chain portions of the molten globule state of a protein (be sure to include how this structure is stabilized)

Answer 23

The globule is compact

The molten side chain structure is primarily stabilized by nonspecific hydrophobic interactions