期刊
BIOCHEMICAL JOURNAL
卷 474, 期 10, 页码 1619-1631出版社
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20170085
关键词
-
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB 08010101]
- National Key Research and Development Program of China [2016YFA0400903]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [31621002]
- National Natural Science Foundation of China [U1532109, 31370756, 31361163002, 31400627]
- Scientific Research Grant of Hefei Science Centre of CAS [2015SRG-HSC043, 2015HSC-UP019]
- Anhui Provincial Natural Science Foundation [1608085QC52]
Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE-CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206-1226), which binds SdrE N2 and N3 domains (SdrE(N2N3)) with high affinity, and determined the crystal structures of apo-SdrE(N2N3) and the SdrE(N2N3)-CFH1206-1226 complex. Comparison of the structure of the CFH-SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrE(N2N3) adopts a 'close' state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel 'close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion.
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