Signaling through C2 domains: More than one lipid target

Abstract

AbstractC2 domains are membrane-binding modules that share a common overall fold: a single compact Greek-key motif organized as an eight-stranded anti-parallel β-sandwich consisting of a pair of four-stranded β-sheets. A myriad of studies have demonstrated that in spite of sharing the common structural β-sandwich core, slight variations in the residues located in the interconnecting loops confer C2 domains with functional abilities to respond to different Ca2+ concentrations and lipids, and to signal through protein–protein interactions as well. This review summarizes the main structural and functional findings on Ca2+ and lipid interactions by C2 domains, including the discovery of the phosphoinositide-binding site located in the β3–β4 strands. The wide variety of functions, together with the different Ca2+ and lipid affinities of these domains, converts this superfamily into a crucial player in many functions in the cell and more to be discovered. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy