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Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel ‘close, dock, lock and latch' mechanism for complement evasion
- Source :
- Biochemical Journal. 474:1619-1631
- Publication Year :
- 2017
- Publisher :
- Portland Press Ltd., 2017.
-
Abstract
- 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 (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3 and the SdrEN2N3–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, SdrEN2N3 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. * C3, : complement component 3; C5, : complement component 5; CCP, : complement-control protein; CFH, : complement factor H; Fg, : fibrinogen; GAG, : glycosaminoglycan; ITC, : isothermal titration calorimetry; LB, : Luria–Bertani; MSCRAMM, : microbial surface component recognizing adhesive matrix molecule; OspE, : outer surface protein E; SdrE, : serine–aspartate repeat protein
- Subjects :
- 0301 basic medicine
Complement component 5
Host cell surface
Complement component 3
C-terminus
Cell Biology
Biology
Ligand (biochemistry)
Biochemistry
eye diseases
Cell biology
03 medical and health sciences
Crystallography
030104 developmental biology
0302 clinical medicine
Factor H
Alternative complement pathway
sense organs
MSCRAMM
Molecular Biology
030215 immunology
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 474
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi...........6a155b6c7a8dc17657cf6390386b970c