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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
#MMPMID28258151
Zhang Y
; Wu M
; Hang T
; Wang C
; Yang Y
; Pan W
; Zang J
; Zhang M
; Zhang X
Biochem J
2017[May]; 474
(10
): 1619-1631
PMID28258151
show ga
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 (CFH(1206-1226)), 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)-CFH(1206-1226) 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.
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