Ligand interactions of the cation-dependent mannose 6-phosphate receptor. Comparison with the cation-independent mannose 6-phosphate receptor.
The interactions of the bovine cation-dependent mannose 6-phosphate receptor with monovalent and divalent ligands have been studied by equilibrium dialysis. This receptor appears to be a homodimer or a tetramer. Each mole of receptor monomer bound 1.2 mol of the monovalent ligands, mannose 6-phosphate and pentamannose phosphate with Kd values of 8 X 10(-6) M and 6 X 10(-6) M, respectively and 0.5 mol of the divalent ligand, a high mannose oligosaccharide with two phosphomonoesters, with a Kd of 2 X 10(-7) M. When Mn2+ was replaced by EDTA in the dialysis buffer, the Kd for pentamannose phosphate was 2.5 X 10(-5) M. By measuring the affinity of the cation-dependent and cation-independent mannose 6-phosphate receptors for a variety of mannose 6-phosphate analogs, we conclude that the 6-phosphate and the 2-hydroxyl of mannose 6-phosphate each contribute approximately 4-5 kcal/mol of Gibb's free energy to the binding reaction. Neither receptor appears to interact substantially with the anomeric oxygen of mannose 6-phosphate. The receptors differ in that the cation-dependent receptor displays no detectable affinity for N-acetylglucosamine 1'-(alpha-D-methylmannopyranose 6-monophosphate) whereas this ligand binds to the cation-independent receptor with a poor, but readily measurable Kd of about 0.1 mM. The spacing of the mannose 6-phosphate-binding sites relative to each other may also differ for the two receptors.
Tong
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Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Kornfeld
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D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent; D002417:Cattle; D002712:Chlorides; D003956:Dialysis; D004492:Edetic Acid / Q000494:pharmacology; D046911:Macromolecular Substances; D008345:Manganese / Q000494:pharmacology*; D017895:Manganese Compounds; D008351:Mannans / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013816:Thermodynamics
D002413:Cations, Divalent; D002712:Chlorides; D046911:Macromolecular Substances; D017895:Manganese Compounds; D008351:Mannans; D008360:Mannosephosphates; D009844:Oligosaccharides; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; C027693:mannose-6-phosphate; D008345:Manganese; C059709:pentamannose phosphate; C048076:methyl 6-(2-acetamido-2-deoxy-alpha-glucopyranosyl phosphate)-alpha-mannopyranoside; D004492:Edetic Acid; C025340:manganese chloride; D000117:Acetylglucosamine