期刊
BIOCHEMICAL JOURNAL
卷 425, 期 -, 页码 501-512出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20090861
关键词
cell signalling; parasite invasion; pathogenesis; presenilin; rhomboid protease; signal peptide peptidase; site-2 protease
资金
- National Institutes of Health [R01AI066025]
- Burroughs-Wellcome Fund
- Packard Foundation
- Howard Hughes Medical Institute
Rhomboid proteases are a fascinating class of enzymes that combine a serine protease active site within the core of all integral membrane protein. Despite having key roles in animal cell signalling and microbial pathogenesis, the membrane-immersed nature of these enzymes had long imposed obstacles to elucidating their biochemical mechanisms. But recent multidisciplinary approaches, including eight crystal structures, four computer simulations and nearly 100 engineered mutants interrogated in vivo and in vitro, are coalescing into an integrated model for one rhomboid orthologue in particular, bacterial GlpG. The protein creates a central hydrated microenvironment immersed below the membrane surface to support hydrolysis by its serine protease-like catalytic apparatus. Four conserved architectural elements in particular act its 'keystones' to stabilize this structure, and the lateral membrane-embedded L1 loop functions as a 'flotation device' to position the protease tilted in the membrane. Complex interplay between lateral substrate gating by rhomboid, substrate unwinding and local membrane thinning leads to intramembrane proteolysis of selected target proteins. Although far from complete, studies with GlpG currently offer the best prospect for achieving a through and sophisticated Understanding of a simplified intramembrane protease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据