Structure of a C-type carbohydrate recognition domain from the macrophage mannose receptor

J Biol Chem. 2000 Jul 14;275(28):21539-48. doi: 10.1074/jbc.M002366200.


The mannose receptor of macrophages and liver endothelium mediates clearance of pathogenic organisms and potentially harmful glycoconjugates. The extracellular portion of the receptor includes eight C-type carbohydrate recognition domains (CRDs), of which one, CRD-4, shows detectable binding to monosaccharide ligands. We have determined the crystal structure of CRD-4. Although the basic C-type lectin fold is preserved, a loop extends away from the core of the domain to form a domain-swapped dimer in the crystal. Of the two Ca(2+) sites, only the principal site known to mediate carbohydrate binding in other C-type lectins is occupied. This site is altered in a way that makes sugar binding impossible in the mode observed in other C-type lectins. The structure is likely to represent an endosomal form of the domain formed when Ca(2+) is lost from the auxiliary calcium site. The structure suggests a mechanism for endosomal ligand release in which the auxiliary calcium site serves as a pH sensor. Acid pH-induced removal of this Ca(2+) results in conformational rearrangements of the receptor, rendering it unable to bind carbohydrate ligands.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Carbohydrate Metabolism*
  • Crystallography, X-Ray
  • Humans
  • Hydrogen-Ion Concentration
  • Lectins / chemistry
  • Lectins, C-Type*
  • Ligands
  • Macrophages / metabolism*
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Rats
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism


  • Lectins
  • Lectins, C-Type
  • Ligands
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Peptide Fragments
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Calcium

Associated data

  • PDB/1EGG
  • PDB/1EGI