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A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands.

DC-SIGN and DC-SIGNR are cell-surface receptors that mediate cell-cell interactions within the immune system by binding to intercellular adhesion molecule-3. The receptor polypeptides share 77% amino acid sequence identity and are type II transmembrane proteins. The extracellular domain of each comprises seven 23-residue tandem repeats and a C-terminal C-type carbohydrate-recognition domain (CRD). Cross-linking, equilibrium ultracentrifugation, and circular dichroism studies of soluble recombinant fragments of DC-SIGN and DC-SIGNR have been used to show that the extracellular domain of each receptor is a tetramer stabilized by an alpha-helical stalk. Both DC-SIGN and DC-SIGNR bind ligands bearing mannose and related sugars through the CRDs. The CRDs of DC-SIGN and DC-SIGNR bind Man(9)GlcNAc(2) oligosaccharide 130- and 17-fold more tightly than mannose, and affinity for a glycopeptide bearing two such oligosaccharides is increased by a further factor of 5- to 25-fold. These results indicate that the CRDs contain extended or secondary oligosaccharide binding sites that accommodate mammalian-type glycan structures. When the CRDs are clustered in the tetrameric extracellular domain, their arrangement provides a means of amplifying specificity for multiple glycans on host molecules targeted by DC-SIGN and DC-SIGNR. Binding to clustered oligosaccharides may also explain the interaction of these receptors with the gp120 envelope protein of human immunodeficiency virus-1, which contributes to virus infection.

Pubmed ID: 11384997


  • Mitchell DA
  • Fadden AJ
  • Drickamer K


The Journal of biological chemistry

Publication Data

August 3, 2001

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Carbohydrate Metabolism
  • Carbohydrate Sequence
  • Cell Adhesion Molecules
  • Cross-Linking Reagents
  • Dimerization
  • Glycolipids
  • Glycopeptides
  • HIV-1
  • Humans
  • Kinetics
  • Lectins
  • Lectins, C-Type
  • Ligands
  • Macromolecular Substances
  • Mannose
  • Membrane Proteins
  • Molecular Sequence Data
  • Monosaccharides
  • Nerve Tissue Proteins
  • Oligosaccharides
  • Peptide Fragments
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Subunits
  • Receptors, Cell Surface