The structure of ligand binding sites has been shown to profoundly influence the evolution of function in homomeric protein complexes. Complexes with multi-chain binding sites (MBSs) have more conserved quaternary structure, more similar binding sites and ligands between homologues, and evolve new functions slower than homomers with single-chain binding sites (SBSs). Here, using in silico analyses of protein dynamics, we investigate whether ligand binding-site structure shapes allosteric signal transduction pathways (STPs), and whether the structural similarity of binding sites influences the evolution of allostery. Our analyses show that: 1) allostery is more frequent among MBS complexes than in SBS complexes, particularly in homomers; 2) in MBS homomers, semi-rigid communities and critical residues frequently connect interfaces and thus they are characterized by STPs that cross protein-protein interfaces, while SBS homomers usually not; 3) ligand binding alters community structure differently in MBS and SBS homomers; 4) allosteric proteins are more likely to have homologs with similar binding site than non-allosteric proteins, suggesting that binding site similarity is an important factor driving the evolution of allostery.
Abrusan, Gyorgy; Marsh, Joseph. (2019). Supplementary data to "Ligand binding site structure shapes allosteric signal transduction and the evolution of allostery in protein complexes" by G. Abrusan and J.A. Marsh, [dataset]. University of Edinburgh. MRC Human Genetics Unit. https://doi.org/10.7488/ds/2493.
|Date made available||4 Feb 2019|