calpain结构活化功能.pdfVIP

Structure, Activation, and Biology of Calpain Koichi Suzuki,1 Shoji Hata,2 Yukiko Kawabata,2 and Hiroyuki Sorimachi2 Variation in the calpain 10 gene has recently been gene or abnormal calpain activity affects susceptibility to shown to be associated with type 2 diabetes by posi- type 2 diabetes, knowledge of the activation mechanism of tional cloning. Since then, studies on calpain 10 have calpain at the molecular level and its physiological func- been started in correlation with diabetes and insulin- tion are essential. In this review, the current status of mediated signaling. In this review, the activation mech- mammalian calpain studies is summarized with reference anism of calpain by calcium ions, which is essential to to calpain 10. understand its physiological functions, is discussed on the basis of recent X-ray structural analyses. Further, special features of the structure of calpain 10 that differ PROPERTIES AND STRUCTURE OF CALPAINS from those of typical - or m-calpain used in most studies are summarized together with discussion of the Calpain is not specific for certain amino acid residues or physiological function of calpain with respect to type 2 sequences but recognizes bonds between domains. As a diabetes. Diabetes 53 (Suppl. 1):S12–S18, 2004 consequence, calpain hydrolyzes substrate proteins in a limited manner, and large fragments retaining intact do- mains are produced by hydrolysis. Calpain is regarded as a