Activation and substrate recognition mechanism of calpain

钙蛋白酶是一种胞内钙依赖的半胱氨酸蛋白酶，被认为通过在一定程度上切割底物蛋白，改变或下调其活性或功能来执行各种生理功能。尽管钙蛋白酶的结构和生化特征已经被很好地定义，但底物专一性或底物识别机制仍有待研究。钙调蛋白是一种内源性钙蛋白酶抑制剂，与钙蛋白酶一样广泛分布。钙蛋白酶和钙调蛋白之间的相互作用是非常特异的，因此这将是一个很好的钙蛋白酶识别底物的模型。研究了钙调蛋白多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。钙离子结合后，可能与钙蛋白酶疏水表面结合的多肽。解决了钙蛋白酶底物--膜联蛋白I的晶体结构问题。在Annexin I的N-尾端被calain切割的位点没有足够的密度来建立模型。改进工作仍在进行中。

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.