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.
Pubmed ID: 19225461 RIS Download
Mesh terms: 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
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