Signaling Networks and Dynamics of Allosteric Transitions in Bacterial Chaperonin GroEL: Implications for Iterative Annealing of Misfolded Proteins

TL;DR

This paper introduces the Structural Perturbation Method (SPM) to map allosteric signaling pathways in the bacterial chaperonin GroEL, linking structural dynamics to its function in protein folding through the Iterative Annealing Mechanism.

Contribution

The study presents a novel application of SPM to identify allosteric wiring in GroEL, connecting structural and dynamical aspects of its allosteric transitions.

Findings

AWD determined from structures drives allosteric transitions

Salt-bridge formation and rupture are key to transitions

Structural and dynamical insights explain GroEL's function

Abstract

Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. They describe the response a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the Structural Perturbation Method (SPM), based on phonon propagation in solids, that can be used to determine the signal transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Applications to the bacterial chaperonin GroEL-GroES complex shows that the AWD determined from structures also drive the allosteric transitions dynamically. Both from a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the Iterative Annealing Mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function in a self-consistent manner.