Nap attack 5

Question 1

protein folding fun facts

Answer 1

the ability of a protein to perform its function depends on its ability to adopt a specific three dimensional structure

• native proteins occupy a lowest energy state
• is a rapid process
• cooperative and reversible
• some spontaneously fold, others require chaperones
• stability comes at the cost of flexibility

Question 2

Proteins fold by

Answer 2

• progressive stabilization of intermediates rather than by random search
• local elements of secondary-structure form guided by the restraints of conformation flexibility and hydrogen-bonding optimization
  
  • adjustments and refinements of these structures to optimize non-covalent associations
  • these elements of secondary structure assemble through longer range interactions

Question 3

for longer proteins

Answer 3

the n-terminal domains may fold before synthesis of the polypeptide is complete

Question 4

cumulative selection

Answer 4

protein folds retain partly correct intermediates because they are slightly more stable than unfolded regions

Question 5

protein stability

Answer 5

tendency to maintain native conformation

Question 6

stability of a protein is

Answer 6

difference in free energies of the folded and unfolded states
lowest free energy usually the one with theh max number of weak interactions

Question 7

Forces that maintain the unfolded state

Answer 7

1) Polypeptide can assume countless conformations, so the unfolded state of a protein is defined by a high degree of conformational entropy
2) Many of the functional groups of unfolded proteins can hydrogen bond with water molecules

Question 8

forces that promote formation of the folded state

Answer 8

1) covalent bonds(disulfides)

2) Non-covalent forces (hydrogen bonds and hydrophobic and ionic interactions)

Question 9

Regions of low protein stability

Answer 9

allow a protein to alter its conformation between multiple states

Question 10

Denaturation

Answer 10

• disruption of native conformation with subsequent loss of biological activity
• energy required quite small = a few hydrogen bonds
• cooperative (too fast to slow down)

Question 11

chaperones

Answer 11

• interact with partially unfolded or improperly folded proteins
• facilitate correct folding pathways
• provide microenvironments where correct folding can occur
  Two families = (Hsp70, chaperonins)

Question 12

Hsp70

Answer 12

• do not actively promote folding
• prevent aggregation of unfolded proteins
• unfolded proteins bind to open ATP bound form of Hsp70
• some of the substrate chains released from the complex will be in native conformation

Question 13

Hsp40

Answer 13

trigger ATP hydrolysis Hsp70 trapping the substrate polypeptide

Question 14

nucleotide exchange factor

Answer 14

promotes dissociation of ADP and recycling of HSP70

Question 15

chaperonins

Answer 15

elaborate protein complexes required for folding of some cellular proteins,
- series of multi sub unit rings form two chambers oriented back-to-back

Question 16

Chaperonin Mechanism

Answer 16

• unfolded protein is first bound hydrophobic surface at apical end
• protein is trapped within the chamber when it is capped by the GroES lid
• GroEL undergoes substantial conformational changes, coupled to ATP hydrolysis that regulate the capping
• within the chamber the polypeptide has about ~10 seconds to fold the time required for atp hydrolysis
• may be bound again if further rounds of folding are required

Question 17

Protein disulfide Isomerase (PDI)

Answer 17

catalyses the interchange of disulfide bonds until the bonds of the native structure are formed
also plays a role in the elimination of folding intermediates with improper disulfides

Question 18

peptide prolyl cis-trans Isomerase (PPI)

Answer 18

catalyzes the interconversion of the cis/trans isomers of Pro peptide bonds