46-kDa mannose 6-phosphate-specific receptor: purification, subunit composition, chemical modification.

A cation-dependent mannose 6-phosphate-specific receptor has recently been isolated from murine P388D1 macrophages and bovine liver (B. Hoflack & S. Kornfeld, (1985) J. Biol. Chem. 260, 12008-12014). The receptor purified from human liver has a subunit molecular size of 43 kDa, is rich in hydrophobic and charged amino acids and contains threonine at the N-terminus. The receptors from human and rat liver are antigenically related. Both are immunologically distinct from the cation-independent 215-kDa mannose 6-phosphate-specific receptor from human liver. Cross-linking experiments indicate that the cation-dependent receptor exists in solution as a tetramer. Modification of arginine and histidine residues, reduced drastically the binding of the receptor to immobilized ligands. Presence of mannose 6-phosphate during modification of arginine residues protected the binding properties of the receptor, suggesting that arginine is a constituent of the mannose 6-phosphate binding site of the receptor. The significance of the inability of histidine-modified receptors to bind ligands remains to be established.