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

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• A cation-dependent mannose 6-phosphate (M6P) receptor has been isolated from murine macrophages and bovine liver.
• The human liver M6P receptor subunit has a molecular size of 43 kDa, is rich in hydrophobic and charged amino acids, and has N-terminal threonine.
• Human and rat liver M6P receptors are antigenically related but distinct from the cation-independent 215-kDa M6P receptor.

Purpose of the Study:

• To characterize the cation-dependent mannose 6-phosphate receptor from human liver.
• To investigate the structural and functional properties of the M6P binding site.
• To elucidate the role of specific amino acid residues in receptor-ligand interactions.

Main Methods:

• Purification of the cation-dependent M6P receptor from human liver.
• Chemical modification of arginine and histidine residues.
• Ligand binding assays using immobilized ligands.
• Cross-linking experiments to determine receptor quaternary structure.

Main Results:

• The cation-dependent M6P receptor exists as a tetramer in solution.
• Modification of arginine and histidine residues significantly reduced ligand binding.
• Protection of arginine residues by M6P during modification preserved receptor binding activity.
• Histidine modification abolished ligand binding, but its functional significance requires further investigation.

Conclusions:

• Arginine residues are integral to the mannose 6-phosphate binding site of the cation-dependent M6P receptor.
• The cation-dependent M6P receptor exhibits distinct immunological and structural properties compared to the cation-independent receptor.
• Further studies are needed to understand the role of histidine in the receptor's function.