Segment spanning residues 727-768 of the complement C3 sequence contains a neoantigenic site and accommodates the binding of CR1, factor H, and factor B

Biochemistry. 1992 Feb 18;31(6):1787-94. doi: 10.1021/bi00121a029.


CR1, CR2, DAF, MCP, factor H, C4bp, factor B, and C3 are members of a family of structurally related molecules, the majority of which belong to the complement system. Several of these molecules also share functional features such as cofactor and decay/dissociation activity and compete with one another in binding to C3b. Since factor H appears to bind to multiple sites in C3, we investigated the relationship between the factor H- and CR1-binding sites in C3b. Factor H binding to C3b is inhibited by either the C3c or C3d fragments, and addition of both fragments together augments this inhibition. One monoclonal anti-C3c antibody, anti-C3-9, which recognizes a neoantigenic epitope expressed upon cleavage to C3 to C3b, inhibited both factor H and CR1 binding to EC3b cells. This monoclonal antibody (MoAb) also inhibited factor B binding to EC3b. Two observations further supported our hypothesis that these molecules bind to proximal sites in C3b. First, a synthetic peptide spanning this region of C3b (C3(727-768)) inhibited factor H binding. Second, antibodies raised against this peptide inhibited binding to CR1, factor H, and factor B to C3b. These data show that H binds to at least two sites in C3b: the site in the C3c fragment is within the identified CR1-binding domain while the site in the C3d fragment surrounds the CR2-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Binding Sites
  • Binding, Competitive
  • Complement C3-C5 Convertases / metabolism*
  • Complement C3b Inactivator Proteins / metabolism*
  • Complement C3c / chemistry*
  • Complement C3c / immunology
  • Complement C3c / metabolism
  • Complement Factor B / metabolism*
  • Complement Factor H
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism


  • Antibodies, Monoclonal
  • Complement C3b Inactivator Proteins
  • Epitopes
  • Peptide Fragments
  • Complement C3c
  • Complement Factor H
  • Complement C3-C5 Convertases
  • Complement Factor B