GroEL‐Mediated protein folding

• Published in: Protein science Vol. 6; no. 4; pp. 743 - 760
• Main Authors: Fenton, Wayne A., Horwich, Arthur L.
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01-04-1997
• Subjects: Adenosine Triphosphate - metabolism; chaperonin; Chaperonin 10 - chemistry; Chaperonin 60 - chemistry; Chaperonin 60 - metabolism; GroES; Hsp60; Hydrolysis; kinetic partitioning; mechanism of action; Peptides - metabolism; Protein Binding; Protein Folding; X‐ray structure
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.5560060401

I
Architecture of GroEL and GroES and the reaction pathway
A.
Architecture of the chaperonins
B.
Reaction pathway of GroEL‐GroES‐mediated folding
II.
Polypeptide binding
A.
A parallel network of chaperones binding polypeptides in vivo
B.
Polypeptide binding in vitro
1.
Role of hydrophobicity in recognition
2.
Homologous proteins with differing recognition—differences in primary structure versus effects on folding pathway
3.
Conformations recognized by GroEL
a.
Refolding studies
b.
Binding of metastable intermediates
c.
Conformations while stably bound at GroEL
4.
Binding constants and rates of association
5.
Conformational changes in the substrate protein associated with binding by GroEL
a.
Observations
b.
Kinetic versus thermodynamic action of GroEL in mediating unfolding
c.
Crossing the energy landscape in the presence of GroEL
III.
ATP binding and hydrolysis—driving the reaction cycle
IV.
GroEL‐GroES‐polypeptide ternary complexes—the folding‐active cis complex
A.
Cis and trans ternary complexes
B.
Symmetric complexes
C.
The folding‐active intermediate of a chaperonin reaction—cis ternary complex
D.
The role of the cis space in the folding reaction
E.
Folding governed by a “timer” mechanism
F.
Release of nonnative polypeptides during the GroEL‐GroES reaction
G.
Release of both native and nonnative forms under physiologic conditions
H.
A role for ATP binding, as well as hydrolysis, in the folding cycle
V.
Concluding remarks