The Structure and Activity Regulation of Calpain

There are two kinds of ubiquitous calpains, calpain Ⅰ and calpain Ⅱ, differing in their Ca~2+ requirements for half maximum activities. Both calpains have a large subunit and a small subunit, with molecular weights of 80 and 30 ku respectively. Large subunit is composed of 4 domains. Small subunit is composed of 2 domains. Recently, several tissue specific calpains were discovered, adding to the complexity of calpain system. Calpastatin is an endogenous suppressor of calpain, which can bind to activated calpain specifically and made them inactive. There are 5 domains in calpastatin, domain L and 4 repeated domains numbered 1 to 4 which are responsible for their inhibity effects. Calpain activity is restrictively regulated in living cells. Membrane attachment reaction can low the Ca~2+ requirement of calpain to be activated. The negatively charged phosphate groups on the polar head of membrane phospholipids are inportment for that activation. Autolysis also can low the Ca~2+ requirement of calpain.