《生命科学》 2010, 22(9): 913-918

g分泌酶结构和功能的研究进展

尹肖雯，刘厚奇*

(第二军医大学组织胚胎学教研室，上海 200433)

摘　要：摘  要：g分泌酶是膜整合蛋白酶复合体，可以切割多种I型跨膜蛋白，近年来由于它与阿尔茨海默病发病密切相关而受到广泛关注。g分泌酶介导的膜内切割是一个非常复杂的过程，这和它复杂的内部结构和作用机制有关。最新的研究表明g分泌酶PS亚基的活性位点附近有一个GXGD结构域，它对于g分泌酶的催化活性有重要作用；摵幌稊的发现使g分泌酶在高度疏水的脂质双分子层内的底物切割成为可能。该文综述了近年来g分泌酶结构和功能的研究进展，阐述了g分泌酶切割淀粉样蛋白前体APP释放淀粉样蛋白Ab的过程，并且指出了g分泌酶结构功能的研究进展对阿尔茨海默病治疗的重要意义。
关键词：g分泌酶；GXGD结构域；含水腔隙；底物切割；阿尔茨海默病

Research progresses on the structure and function of g-secretase

YIN Xiao-wen， LIU Hou-qi*

(Department of Histology and Embryology， Second Military Medical University， Shanghai 200433， China)

Abstract: Abstract: g-secretase is a multiprotein complex responsible for the intramembrane cleavage of type I transmembrane proteins. Research on Alzheimer抯 disease pathogenesis lead to the identification of g-secretase， because it mediates the final proteolytic cleavage， which liberates amyloid b-peptide (Ab)， the major component of senile plaques in the brain of Alzheimer抯 disease patients. It was recently found that a GXGD motif around the active sites of PS is important for the g-secretase-cleavage and the water-containing-cavity made the intramembrane cleavage in the highly hydrophobic environment possible. This article reviews the latest research progresses on the structure and function of g-secretase and the cleavage of APP， which releases Ab. g-secretase is the potential drug target for Alzheimer抯 disease.
Key words: g-secretase; GXGD motif; water-containing-cavity; substrate-cleavage; Alzheimer抯 disease