8_22_16 Protein misfolding and disease

Question 1

Pauling

Answer 1

Protein structure determined by sequence (alpha helices and beta-sheets)

Question 2

Anfisen

Answer 2

Denaturing experiments suggest step-wise protein folding as opposed to automatic

Question 3

Levinthal

Answer 3

Only a few possible conformations are sampled during folding

Question 4

Bryngelson and Wolynes

Answer 4

Amino acid positions maximize correct conformation (principle of minimal frustration)

Question 5

Folding free energy changes

Answer 5

local minima and activation energies (overcome by chaperones)

Question 6

GroEL chaperone

Answer 6

Bacterial barrel enzyme, ATP hydolosis (14x) tries to twist protein into correct conformation, if it doesn’t work quickly, protein degrades

Question 7

Chaperone (general)

Answer 7

matchmaker, trafficking, quality control, protein life, and destroyer

Question 8

Folding

Answer 8

Some spontaneous, some mediated by chaperones

Question 9

Unfolding

Answer 9

needed for degradation, facilitated by chaperones which form proteasomes (Ump1) brings together hydrophobic catatlytic regions

Question 10

Molten globule

Answer 10

almost formed protein, explores lowest energy conformations while excluding oxygen (three models: hierarchical, nucleation-condensation, hydrophobic collapse)

Question 11

RING motif

Answer 11

Metal ion stabilizes post cleavage polypeptides

Question 12

Disulfide bonds

Answer 12

made automatically in sequence, but if not the case facilitated by protein disulfide isomerases

Question 13

ER Lumen

Answer 13

Chaperones function also here, if misfolding occurs here then we get ERAD, or removal of misfolded protein via a proteasome

Question 14

Diseases

Answer 14

CF, amyloid diseases, and prion diseases