Potential for modulation of the hydrophobic effect inside chaperonins.

Abstract:

:Despite the spontaneity of some in vitro protein-folding reactions, native folding in vivo often requires the participation of barrel-shaped multimeric complexes known as chaperonins. Although it has long been known that chaperonin substrates fold upon sequestration inside the chaperonin barrel, the precise mechanism by which confinement within this space facilitates folding remains unknown. We examine the possibility that the chaperonin mediates a favorable reorganization of the solvent for the folding reaction. We discuss the effect of electrostatic charge on solvent-mediated hydrophobic forces in an aqueous environment. Based on these physical arguments, we construct a simple, phenomenological theory for the thermodynamics of density and hydrogen-bond order fluctuations in liquid water. Within the framework of this model, we investigate the effect of confinement inside a chaperonin-like cavity on the configurational free energy of water by calculating solvent free energies for cavities corresponding to the different conformational states in the ATP-driven catalytic cycle of the prokaryotic chaperonin GroEL. Our findings suggest that one function of chaperonins may involve trapping unfolded proteins and subsequently exposing them to a microenvironment in which the hydrophobic effect, a crucial thermodynamic driving force for folding, is enhanced.

journal_name

Biophys J

journal_title

Biophysical journal

authors

England JL,Pande VS

doi

10.1529/biophysj.108.131037

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

3391-9

issue

7

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)78481-9

journal_volume

95

pub_type

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