[Intracellular calci-proteins of low molecular weight]

The role of calcium as an intracellular second messenger is now widely recognized. Upon stimulation of a eukaryotic cell, its cytosolic concentration increases 100 fold from pCa 7 to pCa 5. Calcium effects within the cell are mostly mediated through binding of the ion to low molecular weight proteins that form an evolutionary family including parvalbumin, calmodulin, troponin C, the alkali and regulatory light chains of myosin, the S-100 protein and the vitamin D-dependent intestinal calcium-binding protein. The structural, evolutionary and functional unit of each of these proteins is the calcium-binding domain, made of a 12-residue binding loop flanked on each side by a ca 12-residue long alpha-helix. Calcium binding proteins differ in the number of domains and in the Ca2+-binding properties of the domains. Parvalbumin exhibits two high affinity Ca2+-Mg2+-binding sites involved in the relaxation phase of fast skeletal muscle. In contrast, calmodulin and troponin C exhibit low affinity Ca2+-specific sites that trigger Ca2+-dependent effects. Calcium binding to calmodulin is sequential and ordered and results in a conformational change that enables the protein to interact through a hydrophobic patch with the numerous calmodulin-dependent enzymes. Calmodulin is highly conserved, ubiquitous and multifunctional. It is responsible for the Ca2+ control of cell motility, of energy production through the glycogenolytic pathway, and of the modulation of messengers, amongst which are Ca2+ itself, cAMP and neurotransmitters.