Thermodynamic competition between membrane protein oligomeric states

TL;DR

This paper presents a physical framework explaining how thermodynamic factors like concentration, lipid interactions, and monomer interactions determine the dominant oligomeric states of membrane proteins, influencing their function.

Contribution

It introduces a general thermodynamic model for membrane protein oligomerization, integrating multiple physical factors to explain oligomeric state regulation.

Findings

Dominant oligomeric states depend on protein concentration and lipid interactions.

Lipid bilayer deformations influence oligomerization preferences.

The model predicts regulation of protein function via oligomeric state control.

Abstract

Self-assembly of protein monomers into distinct membrane protein oligomers provides a general mechanism for diversity in the molecular architectures, and resulting biological functions, of membrane proteins. We develop a general physical framework describing the thermodynamic competition between different oligomeric states of membrane proteins. Using the mechanosensitive channel of large conductance as a model system, we show how the dominant oligomeric states of membrane proteins emerge from the interplay of protein concentration in the cell membrane, protein-induced lipid bilayer deformations, and direct monomer-monomer interactions. Our results suggest general physical mechanisms and principles underlying regulation of protein function via control of membrane protein oligomeric state.