Macroglobulin alpha 2

Human α2macroglobulin (hα2M) is a serum glycoprotein that has sequence similarity to other members of the α2M family including complement components C3, C4 and C5. α2M is synthesized as a polypeptide of 1474 amino acids with a signal peptide (23 residues) . The mature protein is a tetramer (720 kDa) of 4 identicalsubunits (180 kDa), which form two disulfide bondlinked-dimers. As a general and irreversible protease inhibitor implicated in many processes, α2M is able to inhibit all four classes of proteases by a unique trapping mechanism. The bait region of hα2M (residues 690-728) contains specific cleavage sites for different proteases. The cleavage of the bait region by a protease induces a conformation change in α2M, which then traps and forms a covalent bond with the protease. The trapped protease remains active against small peptide substrates but loses its ability to interact with large protein substrates or inhibitors.