A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands
| Autor: | D A, Mitchell, A J, Fadden, K, Drickamer |
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| Rok vydání: | 2001 |
| Předmět: |
Macromolecular Substances
Protein Conformation Molecular Sequence Data Oligosaccharides Nerve Tissue Proteins Receptors Cell Surface Ligands Protein Structure Secondary Lectins Humans Lectins C-Type Amino Acid Sequence Binding Sites Base Sequence Monosaccharides Glycopeptides Membrane Proteins Peptide Fragments Kinetics Protein Subunits Cross-Linking Reagents Carbohydrate Sequence HIV-1 Carbohydrate Metabolism Glycolipids Cell Adhesion Molecules Dimerization Mannose |
| Zdroj: | The Journal of biological chemistry. 276(31) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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