Identification of residues in alpha-macroglobulins important for binding to the alpha(2)-macroglobulin receptor low density lipoprotein receptor-related protein

Variants of the receptor binding domain of both human alpha(2)-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 alpha(2)-macroglobulin for binding to the multifunctional alpha(2)-macroglobulin receptor identify two Lys residues (residues 1370 and 1374 in human alpha(2)-macroglobulin) spaced by three amino acid residues as crucial for receptor binding, From this result and mutational evidence from other ligands for the alpha(2)-macroglobulin receptor, a tentative sequence motif for receptor binding is proposed.