Post-translational modification of the fourth component of complement. Sulfation of the alpha-chain.

The fourth component of complement (C4) was found to incorporate radiolabel from [35S]O4 during synthesis in murine peritoneal macrophages and the human hepatoma-derived cell line, HepG2. The sulfate label was localized to the COOH-terminal autolytic fragment of the C4 alpha-chain. No label was seen associated with intracellular pro-C4. The structurally similar third and fifth components of complement, and alpha 2-macroglobulin, did not incorporate labeled sulfate. Tryptic peptides from [35S]O4-labeled C4 alpha-chain were analyzed by reversed phase liquid chromatography and found to elute in a single, homogeneous peak, suggesting a unique sulfation site in the C4 alpha-chain. Thin layer chromatography of a base hydrolysate of [35S]O4-labeled C4 alpha-chains, or C4 isolated from human plasma, revealed the presence of tyrosine-O-sulfate. The possible significance of this unusual amino acid modification for the function of C4 is unknown.