Structural requirements for high affinity binding of complex ligands by the macrophage mannose receptor.
The mannose receptor of macrophage and hepatic endothelial cells discriminates between endogenous and exogenous sugar-bearing structures. Previous competition studies have indicated that the receptor binds the monosaccharides mannose, fucose, and N-acetylglucosamine but displays much higher affinity for multivalent oligosaccharides, such as those found on the surface of potentially pathogenic microorganisms. The hydrodynamic properties of the receptor have been examined, revealing that the receptor is a monomer. This result suggests that multiple carbohydrate recognition domains (CRDs) in the extracellular domain of a single receptor polypeptide cooperate to achieve high affinity binding of complex ligands. In order to determine the importance of individual CRDs, properties of receptor segments containing groups of CRDs expressed in insect cells have been examined. The results indicate that two of the CRDs (4 and 5) form a protease-resistant, ligand-binding core but that five CRDs in tandem (4-8) are required to match the affinity of the intact receptor for yeast mannan. A consequence of the organization of the receptor is that both valency and geometry of glycoconjugates are important determinants of binding affinity.
Taylor
M E
ME
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Drickamer
K
K
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002460:Cell Line; D006031:Glycosylation; D007313:Insecta; D037181:Lectins, C-Type; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection
D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D008358:Mannose