FHBP_NEIMB A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374).[1][2][3][4][5][6][7]
Evolutionary Conservation
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Publication Abstract from PubMed
The complement system is an essential component of the innate and acquired immune system, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.
Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates.,Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Arico B, Brunelli B, Pieri A, Santini L, Savino S, Serruto D, Litt D, Kroll S, Welsch JA, Granoff DM, Rappuoli R, Pizza M. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med. 2003 Mar 17;197(6):789-99. PMID:12642606 doi:10.1084/jem.20021911
↑Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A, Knauf M, Ooi P, Smith RP, Weise P, Wetherell M, Xie X, Zagursky R, Zhang Y, Zlotnick GW. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun. 2004 Apr;72(4):2088-100. PMID:15039331 doi:10.1128/IAI.72.4.2088-2100.2004
↑Giuliani MM, Santini L, Brunelli B, Biolchi A, Aricò B, Di Marcello F, Cartocci E, Comanducci M, Masignani V, Lozzi L, Savino S, Scarselli M, Rappuoli R, Pizza M. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun. 2005 Feb;73(2):1151-60. PMID:15664958 doi:10.1128/IAI.73.2.1151-1160.2005
↑Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM. Functional significance of factor H binding to Neisseria meningitidis. J Immunol. 2006 Jun 15;176(12):7566-75. PMID:16751403 doi:10.4049/jimmunol.176.12.7566
↑Scarselli M, Arico B, Brunelli B, Savino S, Di Marcello F, Palumbo E, Veggi D, Ciucchi L, Cartocci E, Bottomley MJ, Malito E, Lo Surdo P, Comanducci M, Giuliani MM, Cantini F, Dragonetti S, Colaprico A, Doro F, Giannetti P, Pallaoro M, Brogioni B, Tontini M, Hilleringmann M, Nardi-Dei V, Banci L, Pizza M, Rappuoli R. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med. 2011 Jul 13;3(91):91ra62. PMID:21753121 doi:10.1126/scitranslmed.3002234
↑Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM. Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules. PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374 doi:https://dx.doi.org/10.1371/journal.ppat.1002981
↑Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769
↑Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769
