Domain structure of human α2‐macroglobulin

Publisher Website
Google Scholar
Abstract
Digestion of methylamine‐treated α2‐macroglobulin (α2M·MA) with catalytic amounts of papain at pH 4.5 has been investigated. Cleavage of Lys(1313)‐Glu resulted in two major products, which could be separated by gel chromatograhy: a large disulfide bridged fragment set nearly the size of intact α2M·MA, and an 18 kDa fragment, constituting the carboxy‐terminal domain of α2M. This domain contained the receptor recognition site, exposed as a result of cleavage of the internal β‐cysteinyl‐γ‐glutamyl thiol esters in α2M. Compared with α2M‐trypsin complex the apparent affinity for binding to rat hepatocyte receptors was 0.1 and 2% at 4 and 37°C, respectively. The receptor‐binding domain presumably forms a compact globular β‐barrel‐type structure, stable at pH 2.5–9.0. Chemical modification experiments suggest that receptor binding is contributed by a determinant formed by the precise folding of the polypeptide chain.