title: Structural determinants of host specificity of complement Factor H recruitment by Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: David
authors.initials: D
authors.lastname: Achila
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: Aizhuo
authors.initials: A
authors.lastname: Liu
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: Rahul
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: Erik
authors.initials: E
authors.lastname: Martinez-Hackert
authors.affiliation: †Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jing-Ren
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: *Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, U.S.A.
authors.forename: Honggao
authors.initials: H
authors.lastname: Yan
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D046912:Multiprotein Complexes; C110344:SpsA protein, Streptococcus pneumoniae; D037521:Virulence Factors; D017242:Complement Factor H