Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/nature07769

Type

Journal article

Journal

Nature

Publication Date

16/04/2009

Volume

458

Pages

890 - 893

Keywords

Antigens, Bacterial, Bacterial Proteins, Binding Sites, Carbohydrates, Complement Factor H, Crystallography, X-Ray, Ligands, Models, Molecular, Molecular Mimicry, Neisseria meningitidis, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Conformation, Structure-Activity Relationship, Substrate Specificity