title: Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates.
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.
authors.affiliation: Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AZ, UK.
authors.forename: Muriel C
authors.initials: MC
authors.lastname: Schneider
authors.forename: Beverly E
authors.initials: BE
authors.lastname: Prosser
authors.forename: Joseph J E
authors.initials: JJ
authors.lastname: Caesar
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kugelberg
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sadik
authors.initials: S
authors.lastname: Quoraishi
authors.forename: Janet E
authors.initials: JE
authors.lastname: Lovett
authors.forename: Janet E
authors.initials: JE
authors.lastname: Deane
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Steven
authors.initials: S
authors.lastname: Johnson
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lea
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D017242:Complement Factor H / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D009345:Neisseria meningitidis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002241:Carbohydrates; D008024:Ligands; C484699:factor H-binding protein, Neisseria meningitidis; D017242:Complement Factor H