Structural characterization of the murine fourth component of complement and sex-limited protein and their precursors: evidence for two loci in the S region of the H-2 complex.
The S region of the murine major histocompatibility complex controls the expression of two related, serum substance-positive proteins; one (C4) has functional complement activity, whereas the other, the sex-limited protein (Slp), is hemolytically nonfunctional. The structural relationships of these molecules to each other and to their putative intracellular precursors have been examined. Radiolabeled intracellular C4 and Slp precursors were isolated from lysates of cultured peritoneal cells. The C4 and Slp precursors and their processed subunits were purified by immunoprecipitation and sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Antigenically distinct precursors for C4 and Slp were demonstrated by sequential immunoprecipitation experiments in which anti-Slp-reactive molecules were precleared by exhaustive immunoprecipitation and residual C4 molecules were precipitated by antibody to serum substance. Both molecules had apparent molecular weights of 185,000. Their molecular identities as precursors of the mature C4 and Slp proteins were established in pulse-chase studies and by comparisons of their tryptic peptide profiles with those of isolated subunits from the processed proteins. When isolated alpha- or beta-subunits from C4 and Slp proteins were compared by peptide mapping, it was possible to detect multiple distinct and multiple shared peptides. This evidence indicates that the C4 and Slp proteins derive from distinct precursor polypeptides and suggests that the primary structures of the C4 and Slp alpha- and beta-subunits are different. These results support the postulate that the S region contains two discrete structural loci that specify discrete C4 and Slp proteins.
D000818:Animals; D001609:Beta-Globulins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D000939:Epitopes; D005796:Genes; D006183:H-2 Antigens / Q000235:genetics*; D008285:Major Histocompatibility Complex; D051379:Mice; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000235:genetics*; D009626:Terminology as Topic
D001609:Beta-Globulins; D003181:Complement C4; D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments; D011498:Protein Precursors