Structures of C3b in complex with factors B and D give insight into complement convertase formation

Science. 2010 Dec 24;330(6012):1816-20. doi: 10.1126/science.1195821.


Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom resolution and its complex with factor D at 3.5 angstrom resolution. Our data show how factor B binding to C3b forms an open "activation" state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Complement C3 Convertase, Alternative Pathway / chemistry*
  • Complement C3 Convertase, Alternative Pathway / metabolism
  • Complement C3b / chemistry*
  • Complement C3b / metabolism
  • Complement Factor B / chemistry*
  • Complement Factor B / metabolism
  • Complement Factor D / chemistry*
  • Complement Factor D / metabolism
  • Complement Pathway, Alternative
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Mutant Proteins / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary


  • Mutant Proteins
  • Complement C3b
  • Complement Factor D
  • Complement C3 Convertase, Alternative Pathway
  • Complement Factor B

Associated data

  • PDB/2XW9
  • PDB/2XWA
  • PDB/2XWB
  • PDB/2XWJ