High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2

Bider, M. D. and Cescato, R. and Jeno, P. and Spiess, M.. (1995) High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2. European journal of biochemistry, Vol. 230, H. 1. pp. 207-212.

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Official URL: http://edoc.unibas.ch/dok/A5258321

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The hepatic asialoglycoprotein receptor is a hetero-oligomer composed of two homologous subunits. The specificity and affinity of ligand binding depends on the number and spatial arrangement of several galactose-binding sites within the receptor complex. Previous studies indicated that both subunits are required for high-affinity ligand binding, i.e. for the simultaneous interaction with three galactose residues within an N-linked glycan. However, we found that asialoorosomucoid (ASOR) and asialofetuin (ASF) bind to transfected COS-7 cells expressing subunit H1 in the absence of the second subunit H2. ASOR binding occurred with a dissociation constant of approximately 40 nM, approximately four-times higher than the Kd of ASOR binding to the hetero-oligomeric receptor. Normalized to the amount of H1 expressed, approximately 10-times fewer binding sites were produced by H1 alone. A glycopeptide with a single tri-antennary N-linked glycan purified from ASF bound to the hetero-oligomeric receptor, but did not bind detectably to H1-expressing COS-7 cells. H1 is thus unable to simultaneously recognize all three galactose residues in a glycan. From this, we conclude that, at a sufficiently high density of H1 on the cell surface, high-affinity binding of ASOR and ASF is the result of two or more glycans interacting with H1 oligomers with low affinity in a bivalent manner.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spiess)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Mass Spectrometry (Jenö)
UniBasel Contributors:Spiess, Martin and Jenö, Paul
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 06:48
Deposited On:22 Mar 2012 13:20

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