Limited proteolysis of beta 2-microglobulin at Lys-58 by complement component C1s.
We have now demonstrated that activated complement component C1s cleaves beta 2-microglobulin at the position identical to that at which beta 2-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 beta 2-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-beta 2-microglobulin. This is the first demonstration of a noncomplement protein substrate for the proteolytic activity of C1s. The C1s-induced cleavage of beta 2-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 beta 2-microglobulin.
Nissen
M H
MH
Department of Biochemistry, University of Aberdeen, Scotland.
Roepstorff
P
P
Thim
L
L
Dunbar
B
B
Fothergill
J E
JE
D000595:Amino Acid Sequence; D015923:Complement C1r / Q000302:isolation & purification / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008239:Lysine; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000302:isolation & purification; D013379:Substrate Specificity; D001613:beta 2-Microglobulin / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine
D010446:Peptide Fragments; D001613:beta 2-Microglobulin; D015923:Complement C1r; D003173:Complement C1s; D008239:Lysine