Lecture 6 - Folding accessory proteins Flashcards
Proteins often fold in vitro into
quasi-stable non-native conformations
3 types of accessory proteins
- Protein disulfide isomerases (PDI)
- Peptidyl prolyl cis-trans isomerases (PPI)
- Molecular chaperones
When reduced, PDI catalyzes
disulfide interchange reactions
PDI shuffles disulfide bonds until
they achieve their native conformation
Oxidative PDI serves to
introduce new disulfide bonds into folding proteins
_____% of folded proteins contain proline in the cis conformation
10
PPIs catalyze
the interconversion of proline from trans to cis
Newly synthesized and unfolded proteins contain many exposed
hydrophobic groups
Exposed hydrophobic groups in newly synthesized and unfolded proteins are prone to
aggregation and improper folding
Molecular chaperones function to
prevent or reverse improper folding and/or aggregation
Molecular chaperones work by binding to
exposed hydrophobic groups of an unfolded protein
Heat shock protein (Hsp) 70 facilitates
folding of proteins as they are being synthesized by the ribosome
Chaperonins are
large multisubunit proteins that bind hydrophobic patches of partly or improperly folded proteins
A folding protein is enveloped by the chaperonin, thereby protecting it from
aggregation
Chaperonins consist of 2 families
- Hsp60 (GroEL)
- Hsp10 (GreES)
GroEL has _____ identical subunits
14
GroEL has _____ symmetry
D7
GroES forms a dome with _____ identical subunits
7
GroES has ______ symmetry
C7
When GroES caps GroEL, a change in the cis ring of GroEL changes the
volume of the interior
If the folding polypeptide does not reach the native state after interacting with GroEL/ES, it can
bind to GroEL again
A native protein doesn’t bind to GroEL because
a native protein lacks exposed hydrophobic groups
A partly folded polypeptide intermediate is trapped in a local energy minimum, and binding to GroEL
raises its free energy so it can reach the global energy minimum (native state)
