Evolutionary Analysis of Conformational Changes in Allosteric Proteins

Abstract

Allostery is fundamental to control numerous biological processes and coupled to the conformational rearrangements of protein structure. The changes of residue interaction networks upon ligand binding or protein-protein interactions impact protein dynamics and function. General principles on how conformational rearrangements of residues are encoded in protein sequences remain unknown. Here, we show that the residues that are evolutionary coupled with many partners mediate the conformational rearrangement of protein allostery. Highly evolutionarily coupled residues are involved in a dynamic network which participates in the smooth transition of two allosteric states; protein allostery is built up from the interaction rearrangements of these residues. We show that the evolutionary principles of protein conformational change provide the insight into the mechanisms controlling allosteric regulation and propose a new method to identify the key residues involved in the structural transition.