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Title
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Selective sugar binding to the carbohydrate recognition domains of the rat hepatic and macrophage asialoglycoprotein receptors.
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Authors
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S.T.Iobst,
K.Drickamer.
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Ref.
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J Biol Chem, 1996,
271,
6686-6693.
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PubMed id
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Abstract
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Asialoglycoprotein receptors on the surfaces of both hepatocytes and peritoneal
macrophages bind terminal galactose residues of desialylated glycoproteins and
mediate endocytosis and eventual degradation of these ligands. The hepatic
receptor binds oligosaccharides with terminal N-acetylgalactosamine residues
more tightly than ligands with terminal galactose residues, but the macrophage
receptor shows no such differential binding affinity. Carbohydrate recognition
domains from the macrophage receptor and the major subunit of the hepatic
receptor have been expressed in a bacterial system and have been shown to retain
the distinct binding selectivities of the receptors from which they derive.
Binding of a series of N-acyl derivatives of galactosamine suggests that the
2-substituent of these sugars interacts with the surface of the hepatic receptor
with highest affinity binding observed for the N-propionyl derivative. Chimeric
sugar-binding domains have been used to identify three regions of the hepatic
receptor that are essential for establishing selectivity for
N-acetylgalactosamine over galactose. Based on these results and the orientation
of N-acetylgalactosamine when bound to an homologous galactose-binding mutant of
rat serum mannose-binding protein, a fourth region likely to interact with
N-acetylgalactosamine has been identified and probed by site-directed
mutagenesis. The results of these studies define a binding pocket for the
2-substituent of N-acetylgalactosamine in the hepatic asialoglycoprotein
receptor.
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