Lecture 13 - Protein folding

Question 1

what are the zones of flexibility in a protein

Answer 1

N and C terminus (in some proteins)
exposed side chains
any connecting loops

Question 2

what does myoglobin protein bind

Answer 2

heme group
it carries O2

Question 3

what type of group is aheme group and how is it diff to a co-factor

Answer 3

prosthetic group
binds a lot stronger han a co-factor

Question 4

what things is defined 3D shape necassary for

Answer 4

• catalysis = enzyme needs good atomic alignment w/ substrate
• any protein-substrate or protein-protein interactions = molecular recognition

Question 5

what could be a cause of misfolding

Answer 5

mutations

Question 6

what are some consequences of mutations causing misfolding

Answer 6

• loss of function of enzymes or receptors
• toxic aggregates (the misfoldd proteins accumulating)
• abnomral cell morphology
• abnormal collagen assembly, bad connective tissue

Question 7

hypercholeterolaemia and cystic fibrosis are exmaples of what issue cuased by misfolding

Answer 7

mislocalisation
they accumulate in ER, cant get to final destination
causes LOF of enzymes, receptors and tumour suppresors

Question 8

what misfolding issue is usually seen in neurodegenerative diseases (e.g. alzheimers, huntingtons, parkinsons)

Answer 8

toxic aggregates (e.g. amyloid plaques)
intracellular deposits (e.g. inclusion bodies)

Question 9

what is scury caused by

Answer 9

lack of vit C = incorrect folding of collagen

Question 10

what are examples of protein misfolding leading to abnormal cell or tissue morphology

Answer 10

sickle cell anemia
cataracts

Question 11

what are intrinsicallly disordered proteins(IDPs)

Answer 11

not completely folded, but still have biological function

Question 12

what is compositional bias in regards to IDPs

Answer 12

have low proportion of Val, Leu, Ile, Met, Phe, Trp, Tyr
so w/o these, it’s unliekly to form 3D shape
and has few but overrespresented AAs

Question 13

what is coupled folding and binding

Answer 13

when IDP binds to its target, only then will it fold and become stable 3D structure

Question 14

structure of zinc fingers

Answer 14

wihtout DNA, theyre like beads on a string - linked folded domains
when binds DNA, becomes structured

Question 15

what is Levinthal paradox

Answer 15

theoretically, if protein used random conformational search to fold (ie exploring every bidning option)
would take way too long

Question 16

what is solution to Levinthal paradox

Answer 16

unfolded = some regions fold = form MOLTEN GLOBULE, a semi stable intermediate
which comes together and it’s a lot faster

Question 17

equation for thermodynaics of protein folding

Answer 17

change in G (free energy) = change in H (enthalpy) - Temp(K)*change in S (entropy)

Question 18

for a reaction to occur, what does G need to be

Answer 18

negative
either driven by decrease in H (enthalpy) or by increase in S (disorder)

Question 19

what value of enthalpy usually comes with protein folding

Answer 19

-ve
usually exothermic reaction
cuz bonds being formed, eg. H bonds, electrostatic interactions etc.
= favourable

Question 20

what value of entropy usually comes with protein folding

Answer 20

decreasing disorder (so decreased S)
cuz decreases the degrees of freedom
= unfavourable

Question 21

if entropy is getting less disordered and this makes folding unfavourbale, what factor will offset this to allow protein folding to happen

Answer 21

entropy change of displacign the water around the unfolded chain
- water molecules get freed up = increase disorder
= drives protein folding
(hydrophobic effect)

Question 22

what wa refolding experiments done with

Answer 22

ribonuclease
denature it with urea
when denaturing agent removed, it went back to folded

Question 23

what proteins stabilise intermediates in a crowded cell environemtn, minimising protein misfolding and aggregation

Answer 23

chaperones