2W80

Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs 6-7 of human complement factor H

Summary for 2W80

• Entry DOI: 10.2210/pdb2w80/pdb
• Related: 1FHC 1HAQ 1HFH 1KOV 2G7I 2JGW 2JGX 2UWN 2V8E
• Descriptor: COMPLEMENT FACTOR H, FACTOR H BINDING PROTEIN (3 entities in total)
• Functional Keywords: glycoprotein, immune evasion, age-related macular degeneration, innate immunity, immune response, disease mutation, factor h, complement alternate pathway, vaccine candidate, immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P08603
• Total number of polymer chains: 8
• Total formula weight: 164820.42

Authors

Schneider, M.C.,Prosser, B.E.,Caesar, J.J.E.,Kugelberg, E.,Li, S.,Zhang, Q.,Quoraishi, S.,Lovett, J.E.,Deane, J.E.,Sim, R.B.,Roversi, P.,Johnson, S.,Tang, C.M.,Lea, S.M. (deposition date: 2009-01-08, release date: 2009-03-03, Last modification date: 2024-10-09)

Primary citation

Schneider, M.C.,Prosser, B.E.,Caesar, J.J.E.,Kugelberg, E.,Li, S.,Zhang, Q.,Quoraishi, S.,Lovett, J.E.,Deane, J.E.,Sim, R.B.,Roversi, P.,Johnson, S.,Tang, C.M.,Lea, S.M.
Neisseria Meningitidis Recruits Factor H Using Protein Mimicry of Host Carbohydrates.
Nature, 458:890-, 2009

PubMed 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.

PubMed: 19225461
DOI: 10.1038/NATURE07769

Experimental method

X-RAY DIFFRACTION (2.35 Å)