Proteins Inside the HSP60/HSP10 Fold Under a Constant Electric Field: Potential Implications for the Protein Folding Problem.

Abstract

For a protein to perform its biological functions, it must adopt a specific three-dimensional conformation. In addition, many proteins require the assistance of other protein complexes known as chaperonins to fold -i.e., to acquire such a specific conformation-, although the exact mechanisms whereby the chaperonins act and assist the folding process have not been completely determined. In this work, we characterize the physical environment at the interior of the chaperonin HSP60/HSP10 via Molecular Dynamics Simulations. We found that, inside the cavity of the chaperonin (within a region covering much of the cavity's volume), the long-range electrostatic potential presents a structured pattern that, except for small fluctuations, does not change in time. The electrostatic potential generates an electric field that can be modeled, as a first approximation, as constant and unidirectional (E/(V·Å-1)≈-0.0054𝚤^+0.010𝚥^-0.162k^, here the chaperonin's main axis is aligned along k^), which can produce large deformations in the structure of a heated protein (Rhodanese); the long-range approximated E(r) can in fact unfold the Rhodanese, when applied as an external field. Finally, we discuss the possible implications of such an electric field for the protein folding problem, within the context of proteins whose folding is assisted by chaperones. The existence and effects of the electric field are consistent with several theories and experimental observations related to the protein folding problem, in particular with the foldon view.