Evolution of human alpha 2-macroglobulin.
A papain-binding protein (PBP) resembling human alpha 2-macroglobulin (alpha 2M) but of Mr half that of alpha 2M was purified from plaice (Pleuronectes platessa L.) plasma. The plaice protein displayed most of the distinctive inhibitory properties of the human macroglobulin, and was therefore considered, despite its smaller molecular size, to be homologous with alpha 2M. Plaice PBP was shown to consist of four dissimilar subunits; two I chains (Mr 105 000) and two II chains (Mr 90 000). Each of the larger I chains contained a "bait region" sensitive to proteolytic attack by a variety of proteinases, and an autolytic site analogous to the autolytic site of alpha 2M. Subunit I, almost certainly at the autolytic site, formed SDS-stable, covalent links with methylamine or a proportion of the trapped proteinase molecules. A scheme is proposed for the evolution of human alpha 2M from the smaller fish protein, and the possibility of a shared evolutionary origin for alpha 2M and the complement components C3 and C4 is discussed.
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002352:Carrier Proteins / Q000494:pharmacology; D003176:Complement C3; D003181:Complement C4; D005399:Fishes / Q000097:blood*; D006801:Humans; D046911:Macromolecular Substances; D008744:Methylamines / Q000494:pharmacology; D008970:Molecular Weight; D010206:Papain / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D000511:alpha-Macroglobulins / Q000494:pharmacology
D002352:Carrier Proteins; D003176:Complement C3; D003181:Complement C4; D046911:Macromolecular Substances; D008744:Methylamines; D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; D010206:Papain