A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding

Cell. 1993 Mar 26;72(6):857-67. doi: 10.1016/0092-8674(93)90575-b.


A recombinant peptide encoding the CD11b A domain bound 54Mn2+ with a high affinity. Other divalent cations, including Mg2+, Zn2+, Ni2+, Co2+, and Cd2+, but not Ca2+ or Ba2+, competed effectively for Mn2+ binding. Amino acid substitutions within two conserved and noncontiguous regions in the recombinant peptide abolished 54Mn2+ binding. When these substitutions were introduced independently in complement receptor type 3 (CR3), each abolished the metal-dependent binding of the receptor to the major C3 opsonin iC3b, without impairing subunit association or surface expression of the receptor. These findings identify an unsuspected and novel metal-binding site within the A domain of CR3 that is required for metal-dependent ligand binding and also identify a good target for designing drugs aimed at countering the inflammatory potential of this key receptor.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cations
  • Cell Line
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • DNA Mutational Analysis
  • Ligands
  • Macrophage-1 Antigen / chemistry*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Secondary
  • Recombinant Proteins
  • Sequence Alignment
  • Solubility
  • Spectrum Analysis
  • Structure-Activity Relationship


  • Cations
  • Ligands
  • Macrophage-1 Antigen
  • Recombinant Proteins