文章基本信息

标题：Interaction of intramembrane metalloprotease SpoIVFB with substrate Pro-σK
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作者：Sabyasachi Halder ; Daniel Parrell ; Douglas Whitten 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：50
页码：E10677-E10686
DOI：10.1073/pnas.1711467114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Intramembrane proteases (IPs) cleave membrane-associated substrates in nearly all organisms and regulate diverse processes. A better understanding of how these enzymes interact with their substrates is necessary for rational design of IP modulators. We show that interaction of Bacillus subtilis IP SpoIVFB with its substrate Pro-σ^K depends on particular residues in the interdomain linker of SpoIVFB. The linker plus either the N-terminal membrane domain or the C-terminal cystathione-β-synthase (CBS) domain of SpoIVFB was sufficient for the interaction but not for cleavage of Pro-σ^K. Chemical cross-linking and mass spectrometry of purified, inactive SpoIVFB–Pro-σ^K complex indicated residues of the two proteins in proximity. A structural model of the complex was built via partial homology and by using constraints based on cross-linking data. In the model, the Proregion of Pro-σ^K loops into the membrane domain of SpoIVFB, and the rest of Pro-σ^K interacts extensively with the linker and the CBS domain of SpoIVFB. The extensive interaction is proposed to allow coordination between ATP binding by the CBS domain and Pro-σ^K cleavage by the membrane domain.
关键词：intramembrane protease ; regulated intramembrane proteolysis ; Bacillus subtilis ; sporulation ; SpoIVFB