Making the invisible visible: Toward structural characterization of allosteric states, interaction networks, and allosteric regulatory mechanisms in protein kinases

Abstract

Despite the established view of protein kinases as dynamic and versatile allosteric regulatory machines, our knowledge of allosteric functional states, allosteric interaction networks, and the intrinsic folding energy landscapes is surprisingly limited. We discuss the latest developments in structural characterization of allosteric molecular events underlying protein kinase dynamics and functions using structural, biophysical, and computational biology approaches. The recent studies highlighted progress in making the invisible aspects of protein kinase 'life' visible, including the determination of hidden allosteric states and mapping of allosteric energy landscapes, discovery of new mechanisms underlying ligand-induced modulation of allosteric activity, evolutionary adaptation of kinase allostery, and characterization of allosteric interaction networks as the intrinsic driver of kinase adaptability and signal transmission in the regulatory assemblies.