Signatures of protein structure in the cooperative gating of mechanosensitive ion channels

TL;DR

This study investigates how the structure of membrane proteins influences their cooperative gating behavior through membrane-mediated interactions, using MscL channels as a model system.

Contribution

It introduces a modeling approach linking protein structure to cooperative function and membrane interactions, revealing how oligomeric states affect clustering and gating.

Findings

Different oligomeric states lead to distinct clustering behaviors.

Signatures of protein structure are detectable in cooperative gating patterns.

The model quantitatively relates protein shape to cooperative function.

Abstract

Membrane proteins deform the surrounding lipid bilayer, which can lead to membrane-mediated interactions between neighboring proteins. Using the mechanosensitive channel of large conductance (MscL) as a model system, we demonstrate how the observed differences in protein structure can affect membrane-mediated interactions and cooperativity among membrane proteins. We find that distinct oligomeric states of MscL lead to distinct gateway states for the clustering of MscL, and predict signatures of MscL structure and spatial organization in the cooperative gating of MscL. Our modeling approach establishes a quantitative relation between the observed shapes and cooperative function of membrane~proteins.