Quantifying the role of chaperones in protein translocation by computational modelling

TL;DR

This paper uses molecular simulations to quantify how the chaperone Hsp70 facilitates protein import into organelles by analyzing the free-energy landscape and translocation kinetics.

Contribution

It provides a computational model that characterizes the energetic and kinetic role of Hsp70 in protein translocation, based on structural and simulation data.

Findings

Hsp70 significantly lowers the free-energy barrier for translocation.

The model quantifies the kinetics of chaperone-assisted import.

Chaperone binding enhances the efficiency of protein translocation.

Abstract

The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic proteins into organelles, driving their translocation by binding them from the organellar interior. Starting from the experimentally-determined structure of the \textit{E. coli} Hsp70, we computed, by means of molecular simulations, the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process, whose comparison with unassisted translocation highlights the essential role played by Hsp70 in importing cytoplasmic proteins.