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. 1983 Aug;80(16):5061–5065. doi: 10.1073/pnas.80.16.5061

cDNA clone spanning the alpha-gamma subunit junction in the precursor of the murine fourth complement component (C4).

R T Ogata, D C Shreffler, D S Sepich, S P Lilly
PMCID: PMC384188  PMID: 6192448

Abstract

cDNA clones carrying parts of murine fourth complement component (C4, serum substance protein) mRNA sequences have been identified by differential hybridization to mRNA from a high C4-producing strain, B10.WR, and a congeneic low C4 strain, B10.BR, followed by hybrid-selected translation and DNA sequence analysis. One clone, pMLC4/w7-2, encodes an open amino acid reading frame that includes four tandem arginine residues immediately preceding a sequence 85% homologous with the NH2-terminal sequence of the human C4 gamma-chain. The amino acid composition of the predicted sequence upstream of the tandem arginines matches quite closely with the composition of a similar sized peptide at the COOH terminus of the human C4 alpha chain. The latter result raises questions regarding the nature and extent of plasma-mediated postsynthetic processing of the C4 alpha-chain COOH terminus. The results also demonstrate that strain differences in plasma C4 levels (low C4 vs. high C4) reflect differences in steady-state levels of liver C4 mRNA in these strains.

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Selected References

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  1. Bolotin C., Morris S., Tack B., Prahl J. Purification and structural analysis of the fourth component of human complement. Biochemistry. 1977 May 3;16(9):2008–2015. doi: 10.1021/bi00628a039. [DOI] [PubMed] [Google Scholar]
  2. Carroll M. C., Capra J. D. Studies on murine Ss protein: demonstration that S region encodes structural gene for fourth component of complement. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4641–4645. doi: 10.1073/pnas.76.9.4641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carroll M. C., Porter R. R. Cloning of a human complement component C4 gene. Proc Natl Acad Sci U S A. 1983 Jan;80(1):264–267. doi: 10.1073/pnas.80.1.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
  5. Chan A. C., Mitchell K. R., Munns T. W., Karp D. R., Atkinson J. P. Identification and partial characterization of the secreted form of the fourth component of human complement: evidence that it is different from major plasma form. Proc Natl Acad Sci U S A. 1983 Jan;80(1):268–272. doi: 10.1073/pnas.80.1.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Curman B., Ostberg L., Sandberg L., Malmheden-Eriksson I., Stålenheim G., Rask L., Peterson P. A. H-2 linked Ss protein is C4 component of complement. Nature. 1975 Nov 20;258(5532):243–245. doi: 10.1038/258243a0. [DOI] [PubMed] [Google Scholar]
  7. Domdey H., Wiebauer K., Kazmaier M., Müller V., Odink K., Fey G. Characterization of the mRNA and cloned cDNA specifying the third component of mouse complement. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7619–7623. doi: 10.1073/pnas.79.24.7619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dworkin M. B., Dawid I. B. Construction of a cloned library of expressed embryonic gene sequences from Xenopus laevis. Dev Biol. 1980 May;76(2):435–448. doi: 10.1016/0012-1606(80)90392-9. [DOI] [PubMed] [Google Scholar]
  9. Ferreira A., Michaelson J., Nussenzweig V. A polymorphism of the gamma-chain of mouse C4 controlled by the S region of the major histocompatibility complex. J Immunol. 1980 Sep;125(3):1178–1182. [PubMed] [Google Scholar]
  10. Ferreira A., Nussenzweig V., Gigli I. Structural and functional differences between the H-2 controlled Ss and Slp proteins. J Exp Med. 1978 Nov 1;148(5):1186–1197. doi: 10.1084/jem.148.5.1186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fey G., Colten H. R. Biosynthesis of complement components. Fed Proc. 1981 May 15;40(7):2099–2104. [PubMed] [Google Scholar]
  12. Gergen J. P., Stern R. H., Wensink P. C. Filter replicas and permanent collections of recombinant DNA plasmids. Nucleic Acids Res. 1979 Dec 20;7(8):2115–2136. doi: 10.1093/nar/7.8.2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gigli I., von Zabern I., Porter R. R. The isolation and structure of C4, the fourth component of human complement. Biochem J. 1977 Sep 1;165(3):439–446. doi: 10.1042/bj1650439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldberger G., Colten H. R. Precursor complement protein (pro-C4) is converted in vitro to native C4 by plasmin. Nature. 1980 Jul 31;286(5772):514–516. doi: 10.1038/286514a0. [DOI] [PubMed] [Google Scholar]
  15. Gorman J. C., Jackson R., Desantola J. R., Shreffler D., Atkinson J. P. Development of a hemolytic assay for mouse C2 and determination of its genetic control. J Immunol. 1980 Jul;125(1):344–351. [PubMed] [Google Scholar]
  16. Hall R. E., Colten H. R. Cell-free synthesis of the fourth component of guinea pig complement (C4): identification of a precursor of serum C4 (pro-C4). Proc Natl Acad Sci U S A. 1977 Apr;74(4):1707–1710. doi: 10.1073/pnas.74.4.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hansen T. H., Shreffler D. C. Characterization of a constitutive variant of the murine serum protein allotype, Slp. J Immunol. 1976 Nov;117(5 Pt 1):1507–1513. [PubMed] [Google Scholar]
  18. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karp D. R., Parker K. L., Shreffler D. C., Capra J. D. Characterization of the murine C4 precursor (pro-C4): evidence that the carboxy-terminal subunit is the C4 gamma-chain. J Immunol. 1981 May;126(5):2060–2061. [PubMed] [Google Scholar]
  20. Karp D. R., Parker K. L., Shreffler D. C., Slaughter C., Capra J. D. Amino acid sequence homologies and glycosylation differences between the fourth component of murine complement and sex-limited protein. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6347–6349. doi: 10.1073/pnas.79.20.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Karp D. R., Shreffler D. C., Atkinson J. P. Characterization of the Mr difference between secreted murine fourth component of complement and the major plasma form: evidence for carboxyl-terminal cleavage of the alpha chain. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6666–6670. doi: 10.1073/pnas.79.21.6666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klein D., Tewarson S., Figueroa F., Klein J. The minimal length of the differential segment in H-2 congenic lines. Immunogenetics. 1982;16(4):319–328. doi: 10.1007/BF00372303. [DOI] [PubMed] [Google Scholar]
  23. Lachmann P. J., Grennan D., Martin A., Demant P. Identification of Ss protein as murine C4. Nature. 1975 Nov 20;258(5532):242–243. doi: 10.1038/258242a0. [DOI] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Maizels N. Dictyostelium 17S, 25S, and 5S rDNAs lie within a 38,000 base pair repeated unit. Cell. 1976 Nov;9(3):431–438. doi: 10.1016/0092-8674(76)90088-x. [DOI] [PubMed] [Google Scholar]
  26. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Meo T., Krasteff T., Shreffler D. C. Immunochemical characterization of murine H-2 controlled Ss (serum substance) protein through identification of its human homologue as the fourth component of complement. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4536–4540. doi: 10.1073/pnas.72.11.4536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Odink K. G., Fey G., Wiebauer K., Diggelmann H. Mouse complement components C3 and C4. Characterization of their messenger RNA and molecular cloning of complementary DNA for C3. J Biol Chem. 1981 Feb 10;256(3):1453–1458. [PubMed] [Google Scholar]
  29. Parker K. L., Atkinson J. P., Roos M. H., Shreffler D. C. Genetic and structural characterization of H-2-controlled allelic forms of murine C4. Immunogenetics. 1980 Jul;11(1):55–63. doi: 10.1007/BF01567769. [DOI] [PubMed] [Google Scholar]
  30. Parker K. L., Carroll M. C., Shreffler D. C., Capra J. D. Identification of H-2-controlled structural variants of the murine Slp protein and demonstration of cis-regulation of its expression. J Immunol. 1981 Mar;126(3):995–997. [PubMed] [Google Scholar]
  31. Parker K. L., Roos M. H., Shreffler D. C. 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. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5853–5857. doi: 10.1073/pnas.76.11.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Parker K. L., Shreffler D. C., Capra J. D. Partial amino acid sequences of the murine fourth component of complement (C4): demonstration of homology with human C4 and identification of the amino-terminal subunit in pro-C4. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4275–4278. doi: 10.1073/pnas.77.7.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Passmore H. C., Shreffler D. C. A sex-limited serum protein variant in the mouse: inheritance and association with the H-2 region. Biochem Genet. 1970 Jun;4(3):351–365. doi: 10.1007/BF00485752. [DOI] [PubMed] [Google Scholar]
  34. Payvar F., Schimke R. T. Methylmercury hydroxide enhancement of translation and transcription of ovalbumin and conalbumin mRNA's. J Biol Chem. 1979 Aug 25;254(16):7636–7642. [PubMed] [Google Scholar]
  35. Porter R. R., Reid K. B. Activation of the complement system by antibody-antigen complexes: the classical pathway. Adv Protein Chem. 1979;33:1–71. doi: 10.1016/s0065-3233(08)60458-1. [DOI] [PubMed] [Google Scholar]
  36. Press E. M., Gagnon J. Human complement component C4. Structural studies on the fragments derived from C4b by cleavage with C3b inactivator. Biochem J. 1981 Nov 1;199(2):351–357. doi: 10.1042/bj1990351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Quaranta V., Pellegrino M. A., Ferrone S. Serologic and immunochemical characterization of the specificity of four monoclonal antibodies to distinct antigenic determinants expressed on subpopulations of human Ia-like antigens. J Immunol. 1981 Feb;126(2):548–552. [PubMed] [Google Scholar]
  38. Roos M. H., Atkinson J. P., Shreffler D. C. Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: subunit composition, chain size polymorphism, and an intracellular (PRO-Ss) precursor. J Immunol. 1978 Sep;121(3):1106–1115. [PubMed] [Google Scholar]
  39. Roos M. H., Démant P. Murine complement factor B (BF): sexual dimorphism and H-2-linked polymorphism. Immunogenetics. 1982 Jan;15(1):23–30. doi: 10.1007/BF00375499. [DOI] [PubMed] [Google Scholar]
  40. Scheele G., Blackburn P. Role of mammalian RNase inhibitor in cell-free protein synthesis. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4898–4902. doi: 10.1073/pnas.76.10.4898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Shields D., Blobel G. Efficient cleavage and segregation of nascent presecretory proteins in a reticulocyte lysate supplemented with microsomal membranes. J Biol Chem. 1978 Jun 10;253(11):3753–3756. [PubMed] [Google Scholar]
  42. Shreffler D C, Owen R D. A Serologically Detected Variant in Mouse Serum: Inheritance and Association with the Histocompatibility-2 Locus. Genetics. 1963 Jan;48(1):9–25. doi: 10.1093/genetics/48.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Shreffler D. C. The S region of the mouse major histocompatibility complex (H-2): genetic variation and functional role in complement system. Transplant Rev. 1976;32:140–167. doi: 10.1111/j.1600-065x.1976.tb00232.x. [DOI] [PubMed] [Google Scholar]
  44. Villa-Komaroff L., Efstratiadis A., Broome S., Lomedico P., Tizard R., Naber S. P., Chick W. L., Gilbert W. A bacterial clone synthesizing proinsulin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3727–3731. doi: 10.1073/pnas.75.8.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Woods D. E., Markham A. F., Ricker A. T., Goldberger G., Colten H. R. Isolation of cDNA clones for the human complement protein factor B, a class III major histocompatibility complex gene product. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5661–5665. doi: 10.1073/pnas.79.18.5661. [DOI] [PMC free article] [PubMed] [Google Scholar]

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