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2015 ; 465
(2
): 325-35
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Structural determinants of host specificity of complement Factor H recruitment by
Streptococcus pneumoniae
#MMPMID25330773
Achila D
; Liu A
; Banerjee R
; Li Y
; Martinez-Hackert E
; Zhang JR
; Yan H
Biochem J
2015[Jan]; 465
(2
): 325-35
PMID25330773
show ga
Many human pathogens have strict host specificity, which affects not only their
epidemiology but also the development of animal models and vaccines. Complement
Factor H (FH) is recruited to pneumococcal cell surface in a human-specific
manner via the N-terminal domain of the pneumococcal protein virulence factor
choline-binding protein A (CbpAN). FH recruitment enables Streptococcus
pneumoniae to evade surveillance by human complement system and contributes to
pneumococcal host specificity. The molecular determinants of host specificity of
complement evasion are unknown. In the present study, we show that a single human
FH (hFH) domain is sufficient for tight binding of CbpAN, present the crystal
structure of the complex and identify the critical structural determinants for
host-specific FH recruitment. The results offer new approaches to the development
of better animal models for pneumococcal infection and redesign of the virulence
factor for pneumococcal vaccine development and reveal how FH recruitment can
serve as a mechanism for both pneumococcal complement evasion and adherence.