Identification of Residues in α-Macroglobulins Important for Binding to the α2-Macroglobulin Receptor/Low Density Lipoprotein Receptor-related Protein

Variants of the receptor binding domain of both human α2-macroglobulin and the corresponding domain of hen egg white ovomacroglobulin have been expressed in Escherichia coli and refolded in vitro. Competition experiments with methylamine-treated α2-macroglobulin for binding to the multifunctional α2-macroglobulin receptor identify two Lys residues (residues 1370 and 1374 in human α2-macroglobulin) spaced by three amino acid residues as crucial for receptor binding. From this result and mutational evidence from other ligands for the α2-macroglobulin receptor, a tentative sequence motif for receptor binding is proposed. Variants of the receptor binding domain of both human α2-macroglobulin and the corresponding domain of hen egg white ovomacroglobulin have been expressed in Escherichia coli and refolded in vitro. Competition experiments with methylamine-treated α2-macroglobulin for binding to the multifunctional α2-macroglobulin receptor identify two Lys residues (residues 1370 and 1374 in human α2-macroglobulin) spaced by three amino acid residues as crucial for receptor binding. From this result and mutational evidence from other ligands for the α2-macroglobulin receptor, a tentative sequence motif for receptor binding is proposed.