Primary Structure Of α₂-Macroglobulin

The α₂M tetramer of M_r 725,000 consists of four apparently identical single polypeptide chain monomers of M_r 180,000, corresponding to about 1450 amino acid residues. At the present stage of our sequence determination 1383 residues can be accounted for in three segments of continuous sequence namely the N-terminal (residues 1-440); the “middle” of 298; the C-terminal of approx. 645 residues. The eight oligosaccharide prosthetic groups are glucosamine-based and attached to Asn-residues, five in the N- terminal, three in the C-terminal segment. 25 CNBr-frag- ments have been found, 22-Met-residues have been overlapped. 23 Cys-sequences have been determined so far and ten -S-S- bridges identified. The Cys-residue (approx, no. 472 from the C-terminal in each chain) of the sequence is thiol-ester linked to the γ-carboxyl of the Glx-residue in native α₂M which has not been reacted with proteinase or “inactivated” with methylamine or by heat inactivation.

Neither extensive internal sequence homology, nor homology with other proteinase inhibitors of known primary structure has yet been observed.