Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: two ways to promote multifunctionality.
Calcium signaling pathways control a variety of cellular events such as gene transcription, protein phosphorylation, nucleotide metabolism, and ion transport. These pathways often involve a large number of calcium-binding proteins collectively known as the calmodulin or EF-hand protein superfamily. Many EF-hand proteins undergo a large conformational change upon binding to Ca(2+) and target proteins. All members of the superfamily share marked sequence homology and similar structural features required to sense Ca(2+). Despite such structural similarities, the functional diversity of EF-hand calcium-binding proteins is extraordinary. Calmodulin itself can bind >300 different proteins, and the many members of the neuronal calcium sensor and S100 protein families collectively recognize a largely different set of target proteins. Recent biochemical and structural studies of many different EF-hand proteins highlight remarkable similarities and variations in conformational responses to the common ligand Ca(2+) and their respective cellular targets. In this review, we examine the essence of molecular recognition activities and the mechanisms by which calmodulin superfamily proteins control a wide variety of Ca(2+) signaling processes.
Ikura
Mitsuhiko
M
Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. mikura@uhnres.utoronto.ca
Ames
James B
JB
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007477:Ions; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D009711:Nucleotides / Q000737:chemistry; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D009418:S100 Proteins / Q000378:metabolism; D015398:Signal Transduction
D002147:Calmodulin; D007477:Ions; D008024:Ligands; D009711:Nucleotides; D009418:S100 Proteins; D002118:Calcium