Activation and substrate recognition mechanism of calpain

钙蛋白酶是一种胞内钙依赖性半胱氨酸蛋白酶，被认为通过在有限范围内切割底物蛋白并改变或下调底物蛋白的活性或功能来发挥多种生理功能。虽然钙蛋白酶的结构和生化特征已经被很好地定义，但底物特异性或底物识别机制仍有待研究。钙pastatin是一种内源性钙蛋白酶抑制剂，与钙蛋白酶一样普遍存在。calpain和calpastatin之间的相互作用是非常特异性的，因此这将是一个很好的calpain识别底物的模型。研究了钙蛋白酶肽对钙离子和其他金属离子诱导的钙蛋白酶结构变化的影响。在钙离子的结合下暴露在钙蛋白酶疏水表面的多肽。并对钙蛋白酶底物膜联蛋白1的晶体结构进行了分析。calpain在膜联蛋白I n尾切割的位点密度不足，无法建立模型。改进仍在进行中。

Calpain, an itracelular calcium-dependent cystein protease, is thought to perform various physiological functions by cleaving substrate proteins to a limited extent, and altering or down-regulating their activities or functions. Altough the structural and biochemical features of calpains have been well defined, substrate specificity or substrate-recognition mechanism remains to be investigated. Calpastatin, an endogenous calpain inhibitor is distributed ubiquitously as well as calpain. Interaction between calpain and calpastatin is very specific, so this will be a good model for substrate recognition by calpain. Effects of calpastatin peptides against structural changes of calpain induced by calcium ions and other metal ions were investigated. The peptides supposed to bind at hydrophobic surface of calpain exposed by the binding of calcium ions. Crystal structure of annexin I,a substrate of calpain, was also solved. The site cleaved by calpain at N-tail of annexin I did not have enough density to build a model. The refinement is still in progress.