Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation

Structure. 2004 Mar;12(3):371-8. doi: 10.1016/j.str.2004.02.012.

Abstract

Complement factor B is a 90 kDa protein consisting of three domains: a three-module complement control protein, a von Willebrand factor A domain, and a C-terminal serine protease (SP) domain that adopts a default inactive (zymogen) conformation. The interaction between factor B and pathogen-bound C3b is mediated by its A domain, triggering a conformational change in factor B that ultimately creates the "C3 convertase" of the alternative complement pathway. We report the crystal structure of the A domain from factor B and show that it contains an integrin-like MIDAS motif that adopts the "open" conformation typical of integrin-ligand complexes, with an acidic residue (provided by a fortuitous crystal contact) completing the coordination of the metal ion. Modeling studies indicate that the factor B A domain can also adopt the closed conformation, supporting the hypothesis that an "integrin-like switch" is conserved in complement proteins and perhaps in 60 other A domains found within the human proteome.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Complement C2 / genetics
  • Complement Factor B / chemistry*
  • Complement Factor B / genetics
  • Crystallography, X-Ray
  • Integrins / genetics
  • Ligands
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Complement C2
  • Integrins
  • Ligands
  • complement C2, C allele protein
  • Complement Factor B

Associated data

  • PDB/1Q0P