位点2蛋白酶的结构域、功能与作用机制研究进展

Domain,mechanism and function insights into site-2 proteases

膜内蛋白酶对跨膜蛋白的不可逆性切割过程在跨膜信号转导途径中起着重要作用。位点2蛋白酶(site-2 proteases,S2P)属于膜内蛋白酶中的金属蛋白酶家族。基于进化树的序列分析,S2P及其同源物可以分为亚组Ⅰ至亚组Ⅳ,亚组Ⅰ包括了绝大多数真核生物和细菌的S2P及其同源物,亚组Ⅲ则为少数原核生物如枯草芽孢杆菌和古细菌如詹氏甲烷球菌的S2P同源物。由于S2P参与的信号转导从细菌到人类均具有保守性,本文以亚组Ⅰ和亚组Ⅲ的S2P为例进行综述,阐明S2P及其同源物对跨膜蛋白的切割过程,并展望尚待研究的方向。

By non-reversibly cleaving transmembrane proteins,intramembrane cleaving proteases play important roles in a variety of signaling pathways.Site-2 proteases(S2P)belongs to the metalloprotease family of intramembrane proteases.Based on phylogenetic tree analysis,S2P and its homologs can be divided into subgroups I to IV.Most of S2P and its homologs in eukaryotic and bacterial belong to subgroup I,and a few of S2P homologues in prokaryotes such as Bacillus subtilis and archaea including Methanococcus jannaschii belong to subgroup III.As signaling mechanism is conserved from bacteria to humans,S2P of subgroup I and subgroup III are reviewed as examples in the paper.The cleavage process of transmembrane proteins by S2P and its homologues are elucidated,and the direction of S2P further research are prospected.