Post-translational modification of the fourth component of complement. Sulfation of the α-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 α-chain. No label was seen associated with intracellular pro-C4. The structurally similar third and fifth components of complement, and α₂-macroglobulin, did not incorporate labeled sulfate. Tryptic peptides from [³⁵S]O₄-labeled C4 α-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 α-chain. Thin layer chromatography of a base hydrolysate of [³⁵S]O₄-labeled C4 α-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.