Module 4: Protein folding

Question 1

phi

Answer 1

angle b/w N and alpha-C

Question 2

Psi

Answer 2

angle b/w alpha-C and carbonyl

Question 3

Ramachandran plot

Answer 3

visualize which combo of phi, psi, angles are statically allowed in protein structure

Question 4

Alpha Helix

Answer 4

coil
R groups protrude outward
single turn: 3.6 residues/turn
stabilized by HBs b/w H attached to N atom of peptide linkage and carbonyl of fourth aa on amino terminal side
results in all amide groups pointing to N-terminal and all carbonyl pointing to C terminal

Question 5

What aa is most likely to form an alpha helix?

Answer 5

alanine

Question 6

Beta sheet

Answer 6

formed by single beta strands lined up side-by-side (either antiparallel/parallel)
held by HBs -carbonyl O of one beta sheet H-bonded to H attached to amine on adjacent beta sheet)

Question 7

Once pr- folded, what happens to entropy?

Answer 7

First, entropy decreases
- primary structures would be surrounded by rotationally constrained water molecules (fewer conformations=lower entropy)
Upon protein folding a lot of the hydrophobic residues are buried in the protein core and are interacting with one another-water released/free to tumble around=increase in entropy

Question 8

Motif

Answer 8

recognizable folding pattern involving two or more elements of secondary structure and the connection(s) between them

Question 9

Domain

Answer 9

part of a polypeptide chain that is independently stable or could undergo movements as a single entity with respect to the entire protein
typically large pr-

Question 10

Fibrous Protein

Answer 10

structural roles in cells/tissue
elongated/filamentous in shape
collagen/keratin=long-lasting, resistant to degradation/modification

Question 11

Globular Protein

Answer 11

carry out synthesis, transport, metabolism
very compact structures
bury hydrophobic aa in core and hydrophilic/polar aa on surface

Question 12

Membrane Proteins

Answer 12

use high hydrophobic aa area to interact w hydrophobic acyl chains of lipid bilayer
- rest on top of bilayer (peripheral membrane pr-)/fully integrated (integral membrane pr-)

Question 13

Electrostatic forces

Answer 13

strong
charge-charge
long distance interactions
strength can be weakened on surface of pr- due to water and its larger dielectric constant

Question 14

Hydrogen bonds

Answer 14

usually occur b/w peptide groups and water on pr- surface
in pr- core, occurs b/w peptide groups
highly directional

Question 15

Van der Waals

Answer 15

short interaction range (almost in contact)
very influential when lots
also have corresponding repulsive forces

Question 16

Hydrophobic effect

Answer 16

hydrophobic groups have tendency to cluster together in pr- interior to exclude water
hydrophobic group in water reduces # of HBs free water mol make=thermo unfavourable
thus, water becomes more ordered around hydrophobic mol to conserve HBs and decrease entropy=energetically unfavourable

Question 17

Cooperativity

Answer 17

Pr- highly cooperative w respect to folding

Question 18

Collagen

Answer 18

about 1/4 of all pr-, structural pr-
strengthens tendons and support skin and internal organs
composed of 3 chains in tight triple helix
over 1400 aa long

Question 19

Hemoglobin

Answer 19

composed of 2 alpha chains and 2 beta chains -each w ring-like heme group containing iron
once 1 heme bind oxygen, it nudges neighbours to change shape making them more susceptible to bind oxygen

Question 20

Myoglobin

Answer 20

small, bright red pr-
common in muscle cells
stores oxygen for muscles
contains heme group

Question 21

ATP Synthase

Answer 21

composed of two rotary motors: F0 (electric motor) embedded in membrane and F1 (chemical motor) powered by ATP
F0 motor uses the power from a proton gradient to force the F1 motor to generate ATP

Question 22

F1 structure

Answer 22

uses the power of rotational motion to build ATP, or when operating as a motor, it breaks down ATP to spin the axle the opposite direction
synthesis of ATP: binding of ADP and phosphate, the formation of the new phosphate-phosphate bond, and release of ATP (diff conformations for each step)

Question 23

F0 structure

Answer 23

rotor is composed of 12 identical protein chains

pump has an arginine amino acid that hands off a hydrogen ion to aspartates on the rotor

Question 24

Insulin Receptor

Answer 24

When blood glucose levels rise, beta cells in the pancreas release insulin=uptake of glucose

large protein that binds to insulin and passes its message into the cell
have two tyrosine kinases: when insulin not present, held in a constrained position, but when insulin binds, these constraints are released

Question 25

Type I diabetes vs type II

Answer 25

Type I: pancreatic cells that produce insulin are destroyed by autoimmunity, or insulin is mutated and inactive
Type II: acquired resistance to the action of insulin on its receptor