The predominant form of the fourth component of complement in human and murine plasma (C4(p)) has an M(r) ~5,000 less than C4 secreted by hepatocytes or macrophages (C4(s)). Here we demonstrate that the difference in M(r) results from excision of a peptide from the COOH terminus of the α-chain of C4(s). The site of truncation of the α-chain of C4 in plasma was established by sequence analysis of the COOH-terminal cyanogen bromide fragment isolated by high performance liquid chromatography. Sequential Edman degradation, digestion with carboxypeptidase Y, analysis of amino acid composition, and partial sequence analysis of an overlapping tryptic peptide established the sequence of this peptide to be Glu-Ala-Asn-Glu-Asp-Tyr-Glu-Asp-Tyr-Glu-Tyr-Asp-Glu-Leu-Pro- Ala. Comparison of our results with reported sequences establishes the COOH-terminal alanine to be residue 748 in the α-chain. This identifies the site at which C4(s) is cleaved by an extracellular protease and suggests that the protease has an elastase-like activity.
|Number of pages||5|
|Journal||Journal of Biological Chemistry|
|State||Published - 1986|