Deciphering complement receptor type 1 interactions with recognition proteins of the lectin complement pathway

J Immunol. 2013 Apr 1;190(7):3721-31. doi: 10.4049/jimmunol.1202451. Epub 2013 Mar 4.


Complement receptor type 1 (CR1) is a membrane receptor expressed on a wide range of cells. It is involved in immune complex clearance, phagocytosis, and complement regulation. Its ectodomain is composed of 30 complement control protein (CCP) modules, organized into four long homologous repeats (A-D). In addition to its main ligands C3b and C4b, CR1 was reported to interact with C1q and mannan-binding lectin (MBL) likely through its C-terminal region (CCP22-30). To decipher the interaction of human CR1 with the recognition proteins of the lectin complement pathway, a recombinant fragment encompassing CCP22-30 was expressed in eukaryotic cells, and its interaction with human MBL and ficolins was investigated using surface plasmon resonance spectroscopy. MBL and L-ficolin were shown to interact with immobilized soluble CR1 and CR1 CCP22-30 with apparent dissociation constants in the nanomolar range, indicative of high affinity. The binding site for CR1 was located at or near the MBL-associated serine protease (MASP) binding site in the collagen stalks of MBL and L-ficolin, as shown by competition experiments with MASP-3. Accordingly, the mutation of an MBL conserved lysine residue essential for MASP binding (K55) abolished binding to soluble CR1 and CCP22-30. The CR1 binding site for MBL/ficolins was mapped to CCP24-25 of long homologous repeat D using deletion mutants. In conclusion, we show that ficolins are new CR1 ligands and propose that MBL/L-ficolin binding involves major ionic interactions between conserved lysine residues of their collagen stalks and surface exposed acidic residues located in CR1 CCP24 and/or CCP25.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carrier Proteins / metabolism
  • Complement Pathway, Mannose-Binding Lectin* / genetics
  • Ficolins
  • Humans
  • Kinetics
  • Lectins / metabolism
  • Mannose-Binding Lectin / metabolism*
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Receptors, Complement / chemistry
  • Receptors, Complement / genetics
  • Receptors, Complement / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Carrier Proteins
  • Lectins
  • Mannose-Binding Lectin
  • Receptors, Complement
  • Recombinant Proteins
  • Mannose-Binding Protein-Associated Serine Proteases