Signaling through C2 domains: more than one lipid target.
C2 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 Ca(2+) concentrations and lipids, and to signal through protein-protein interactions as well. This review summarizes the main structural and functional findings on Ca(2+) 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 Ca(2+) 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.
Departamento de Bioquímica y Biología Molecular-A, Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, 30100 Murcia, Spain. Electronic address: senena@um.es.
Senena
S
Corbalan-Garcia
Departamento de Bioquímica y Biología Molecular-A, Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, 30100 Murcia, Spain. Electronic address: jcgomez@um.es.
Juan C
JC
Gómez-Fernández
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D008563:Membrane Lipids; D011493:Protein Kinase C; D002118:Calcium
C2 domain; Ca(2+)-signaling protein; Phosphatidylinositol-4,5-bisphosphate; Signaling domain