Limited proteolysis of β2‐microglobulin at Lys‐58 by complement component C1s

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Abstract
We have now demonstrated that activated complement component C1s cleaves β2‐microglobulin at the position identical to that at which β2‐microglobulin is cleaved in serum of patients suffering from lung cancer. The main cleavage is in the disulphide loop C‐terminal to Lys‐58, generating a modified form of β2‐microglobulin with a two‐chain structure. The C‐terminal Lys‐58 in the A chain is highly susceptible to removal by a carboxypeptidase‐B‐like activity causing the formation of des‐Lys58 ‐β2‐microglobulin. This is the first demonstration of a non‐complement protein substrate for the proteolytic activity of C1s. The C1s‐induced cleavage of β2‐microglobulin can be inhibited in the presence of C1 esterase inhibitor, demonstrating a regulatory function of C1 esterase inhibitor in the C1s‐induced cleavage of β2‐microglobulin.