Identification of residues in alpha-macroglobulins involved in activation of the alpha(2)-macroglobulin signaling receptor

Site-directed mutagenesis of residues in the receptor binding fragment of rat alpha(1)-macroglobulin identify residues 1377 and 1378 (human numbering) as crucial for interaction with the alpha(2)M signaling receptor on murine macrophages. Secondary structure prediction and signaling studies with the mutant proteins suggest the alpha(1)M signaling receptor binding site involves part of a loop-helix-loop motif comprised of residues 1372-1378.