The self-assembly and evolution of homomeric protein complexes

TL;DR

This paper presents a simple model to understand how homomeric protein complexes self-assemble and evolve, explaining recent experimental observations about their stability, interaction strength, and assembly pathways.

Contribution

It introduces a patchy particle model that rationalizes the thermodynamics and dynamics of homomeric protein complex assembly and evolution.

Findings

Evolutionarily newer interactions tend to be weaker.

Subcomplexes with stronger interactions are thermodynamically stable upon destabilization.

Self-assembly is hierarchical with subcomplexes as kinetic intermediates.

Abstract

We introduce a simple "patchy particle" model to study the thermodynamics and dynamics of self-assembly of homomeric protein complexes. Our calculations allow us to rationalize recent results for dihedral complexes. Namely, why evolution of such complexes naturally takes the system into a region of interaction space where (i) the evolutionarily newer interactions are weaker, (ii) subcomplexes involving the stronger interactions are observed to be thermodynamically stable on destabilization of the protein-protein interactions and (iii) the self-assembly dynamics are hierarchical with these same subcomplexes acting as kinetic intermediates.