Neisseria Meningitidis Recruits Factor H Using Protein Mimicry of Host Carbohydrates

Nature. 2009 Apr 16;458(7240):890-3. doi: 10.1038/nature07769. Epub 2009 Feb 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Carbohydrates
  • Ligands
  • factor H-binding protein, Neisseria meningitidis
  • Complement Factor H

Associated data

  • PDB/2W80
  • PDB/2W81