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Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates

DOI: 10.1038/nature07769 DOI Help
PMID: 19225461 PMID Help

Authors: Muriel C Schneider (Centre for Molecular Microbiology and Infection, Imperial College, London) , Beverly E Prosser (Sir William Dunn School of Pathology, University of Oxford) , Joe Caesar (University of Oxford) , Elisabeth Kugelberg (Centre for Molecular Microbiology and Infection, Imperial College, London) , S Li (Centre for Molecular Microbiology and Infection, Imperial College, London) , S Zhang (Centre for Molecular Microbiology and Infection, Imperial College, London) , Sadik Quoraishi (Sir William Dunn School of Pathology, University of Oxford) , Janet E. Lovett (Sir William Dunn School of Pathology, University of Oxford) , Janet E Deane (Sir William Dunn School of Pathology, University of Oxford) , Robert B Sim (MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford) , Pietro Roversi (University of Oxford) , Steven Johnson (University of Oxford) , Christina Tang (University of Oxford) , Susan Lea (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 458 , PAGES 890-893

State: Published (Approved)
Published: February 2009

Abstract: 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.

Journal Keywords: Bacterial; Bacterial; Binding; Carbohydrates; Complement; Crystallography; X-Ray; Ligands; Models; Molecular; Neisseria; Nuclear; Biomolecular; Protein; Structure-Activity; Substrate Specificity

Subject Areas: Medicine


Instruments: I03-Macromolecular Crystallography