Potential for modulation of the hydrophobic effect inside chaperonins

TL;DR

This paper explores how chaperonins may facilitate protein folding by modulating the hydrophobic effect through solvent reorganization within their cavities, based on a physical model of water thermodynamics.

Contribution

It introduces a phenomenological theory linking chaperonin confinement to enhanced hydrophobic interactions via solvent reorganization, providing a new physical perspective on chaperonin function.

Findings

Chaperonins may enhance the hydrophobic effect by altering solvent properties.

Confinement within chaperonins affects water density and hydrogen bonding.

The model suggests a thermodynamic basis for chaperonin-assisted folding.

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. In this study, we examine the possibility that the chaperonin mediates a favorable reorganization of the solvent for the folding reaction. We begin by discussing the effect of electrostatic charge on solvent-mediated hydrophobic forces in an aqueous environment. Based on these initial 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 within 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 be to trap unfolded proteins and subsequently expose them to a micro-environment in which the hydrophobic effect, a crucial thermodynamic driving force for folding, is enhanced.