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.
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
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
J. Biol. Chem.
Date: Aug. 03, 2001
PubMed ID: 11384997
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