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. 1989 Oct 15;263(2):463–469. doi: 10.1042/bj2630463

The quaternary structure in solution of human complement subcomponent C1r2C1s2.

S J Perkins 1, A S Nealis 1
PMCID: PMC1133451  PMID: 2556995

Abstract

C1r2C1s2 is a subcomponent of first component C1 of the complement cascade. Previously two distinct models for its structure have been described, in which C1r2C1s2 is either a linear rod-like assembly of the globular domains found in each of C1s and C1r, or these domains are arranged to form an asymmetric X-shaped structure. These two models were evaluated by using hydrodynamic simulations and neutron scattering. The data on C1s, C1s2 and C1r are readily represented by straight hydrodynamic cylinders, but not C1r2 or C1r2C1s2. Tests of the X-structure for C1r2 and C1r2C1s2 successfully predicted the experimental sedimentation coefficients, thus supporting this model. Neutron scattering analyses on C1s and C1r2 are consistent with a linear structure for C1s, but not for C1r2. An X-shaped structure for C1r2 was found to give a good account of the neutron data at large scattering angles. The total length of the C1s and C1r monomers was determined as 17-20 nm, which is compatible with electron microscopy. On the basis of the known sequences of C1r and C1s, this length is accounted for by a linear arrangement of a serine-proteinase domain (length 4 nm), two short consensus repeat domains (2 x 4 nm), and a globular entity containing the I, II and III domains (4-7 nm).

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Selected References

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  1. Arlaud G. J., Gagnon J. Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r. Biochemistry. 1983 Apr 12;22(8):1758–1764. doi: 10.1021/bi00277a003. [DOI] [PubMed] [Google Scholar]
  2. Arlaud G. J., Gagnon J., Villiers C. L., Colomb M. G. Molecular characterization of the catalytic domains of human complement serine protease C1r. Biochemistry. 1986 Sep 9;25(18):5177–5182. doi: 10.1021/bi00366a029. [DOI] [PubMed] [Google Scholar]
  3. Arlaud G. J., Sim R. B., Duplaa A. M., Colomb M. G. Differential elution of Clq, Clr and Cls from human Cl bound to immune aggregates. Use in the rapid purification of Cl subcomponents. Mol Immunol. 1979 Jul;16(7):445–450. doi: 10.1016/0161-5890(79)90069-5. [DOI] [PubMed] [Google Scholar]
  4. Arlaud G. J., Villiers C. L., Chesne S., Colomb M. G. Purified proenzyme C1r. Some characteristics of its activation and subsequent proteolytic cleavage. Biochim Biophys Acta. 1980 Nov 6;616(1):116–129. doi: 10.1016/0005-2744(80)90269-7. [DOI] [PubMed] [Google Scholar]
  5. Arlaud G. J., Willis A. C., Gagnon J. Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r. Biochem J. 1987 Feb 1;241(3):711–720. doi: 10.1042/bj2410711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bode W., Schwager P. The refined crystal structure of bovine beta-trypsin at 1.8 A resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0. J Mol Biol. 1975 Nov 15;98(4):693–717. doi: 10.1016/s0022-2836(75)80005-2. [DOI] [PubMed] [Google Scholar]
  7. Boyd J., Burton D. R., Perkins S. J., Villiers C. L., Dwek R. A., Arlaud G. J. Neutron scattering studies of the isolated C1r2C1s2 subunit of first component of human complement in solution. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3769–3773. doi: 10.1073/pnas.80.12.3769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Busby T. F., Ingham K. C. Calcium-sensitive thermal transitions and domain structure of human complement subcomponent C1r. Biochemistry. 1987 Aug 25;26(17):5564–5571. doi: 10.1021/bi00391a052. [DOI] [PubMed] [Google Scholar]
  9. Carter P. E., Dunbar B., Fothergill J. E. Structure and activity of C1r and C1s. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):293–299. doi: 10.1098/rstb.1984.0090. [DOI] [PubMed] [Google Scholar]
  10. Chothia C. Structural invariants in protein folding. Nature. 1975 Mar 27;254(5498):304–308. doi: 10.1038/254304a0. [DOI] [PubMed] [Google Scholar]
  11. Cooke R. M., Wilkinson A. J., Baron M., Pastore A., Tappin M. J., Campbell I. D., Gregory H., Sheard B. The solution structure of human epidermal growth factor. 1987 May 28-Jun 3Nature. 327(6120):339–341. doi: 10.1038/327339a0. [DOI] [PubMed] [Google Scholar]
  12. Cooper N. R. The classical complement pathway: activation and regulation of the first complement component. Adv Immunol. 1985;37:151–216. doi: 10.1016/s0065-2776(08)60340-5. [DOI] [PubMed] [Google Scholar]
  13. De La Torre J. G., Bloomfield V. A. Hydrodynamics of macromolecular complexes. III. Bacterial viruses. Biopolymers. 1977 Aug;16(8):1779–1793. doi: 10.1002/bip.1977.360160813. [DOI] [PubMed] [Google Scholar]
  14. Garcia de la Torre J. G., Bloomfield V. A. Hydrodynamic properties of complex, rigid, biological macromolecules: theory and applications. Q Rev Biophys. 1981 Feb;14(1):81–139. doi: 10.1017/s0033583500002080. [DOI] [PubMed] [Google Scholar]
  15. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  16. Journet A., Tosi M. Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r. Biochem J. 1986 Dec 15;240(3):783–787. doi: 10.1042/bj2400783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lacroix M. B., Aude C. A., Arlaud G. J., Colomb M. G. Isolation and functional characterization of the proenzyme form of the catalytic domains of human C1r. Biochem J. 1989 Feb 1;257(3):885–891. doi: 10.1042/bj2570885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leytus S. P., Kurachi K., Sakariassen K. S., Davie E. W. Nucleotide sequence of the cDNA coding for human complement C1r. Biochemistry. 1986 Aug 26;25(17):4855–4863. doi: 10.1021/bi00365a020. [DOI] [PubMed] [Google Scholar]
  19. Mackinnon C. M., Carter P. E., Smyth S. J., Dunbar B., Fothergill J. E. Molecular cloning of cDNA for human complement component C1s. The complete amino acid sequence. Eur J Biochem. 1987 Dec 15;169(3):547–553. doi: 10.1111/j.1432-1033.1987.tb13644.x. [DOI] [PubMed] [Google Scholar]
  20. Medved L. V., Busby T. F., Ingham K. C. Calorimetric investigation of the domain structure of human complement Cl-s: reversible unfolding of the short consensus repeat units. Biochemistry. 1989 Jun 27;28(13):5408–5414. doi: 10.1021/bi00439a014. [DOI] [PubMed] [Google Scholar]
  21. Perkins S. J., Haris P. I., Sim R. B., Chapman D. A study of the structure of human complement component factor H by Fourier transform infrared spectroscopy and secondary structure averaging methods. Biochemistry. 1988 May 31;27(11):4004–4012. doi: 10.1021/bi00411a017. [DOI] [PubMed] [Google Scholar]
  22. Perkins S. J. Molecular modelling of human complement subcomponent C1q and its complex with C1r2C1s2 derived from neutron-scattering curves and hydrodynamic properties. Biochem J. 1985 May 15;228(1):13–26. doi: 10.1042/bj2280013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Perkins S. J. Protein volumes and hydration effects. The calculations of partial specific volumes, neutron scattering matchpoints and 280-nm absorption coefficients for proteins and glycoproteins from amino acid sequences. Eur J Biochem. 1986 May 15;157(1):169–180. doi: 10.1111/j.1432-1033.1986.tb09653.x. [DOI] [PubMed] [Google Scholar]
  24. Perkins S. J. Structural studies of proteins by high-flux X-ray and neutron solution scattering. Biochem J. 1988 Sep 1;254(2):313–327. doi: 10.1042/bj2540313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perkins S. J., Weiss H. Low-resolution structural studies of mitochondrial ubiquinol:cytochrome c reductase in detergent solutions by neutron scattering. J Mol Biol. 1983 Aug 25;168(4):847–866. doi: 10.1016/s0022-2836(83)80078-3. [DOI] [PubMed] [Google Scholar]
  26. Reid K. B. Activation and control of the complement system. Essays Biochem. 1986;22:27–68. [PubMed] [Google Scholar]
  27. Schumaker V. N., Zavodszky P., Poon P. H. Activation of the first component of complement. Annu Rev Immunol. 1987;5:21–42. doi: 10.1146/annurev.iy.05.040187.000321. [DOI] [PubMed] [Google Scholar]
  28. Sim R. B., Porter R. R., Reid K. B., Gigli I. The structure and enzymic activities of the C1r and C1s subcomponents of C1, the first component of human serum complement. Biochem J. 1977 May 1;163(2):219–227. doi: 10.1042/bj1630219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Strang C. J., Siegel R. C., Phillips M. L., Poon P. H., Schumaker V. N. Ultrastructure of the first component of human complement: electron microscopy of the crosslinked complex. Proc Natl Acad Sci U S A. 1982 Jan;79(2):586–590. doi: 10.1073/pnas.79.2.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tosi M., Duponchel C., Meo T., Julier C. Complete cDNA sequence of human complement Cls and close physical linkage of the homologous genes Cls and Clr. Biochemistry. 1987 Dec 29;26(26):8516–8524. doi: 10.1021/bi00400a004. [DOI] [PubMed] [Google Scholar]
  31. Tschopp J., Villiger W., Fuchs H., Kilchherr E., Engel J. Assembly of subcomponents C1r and C1s of first component of complement: electron microscopic and ultracentrifugal studies. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7014–7018. doi: 10.1073/pnas.77.12.7014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Villiers C. L., Arlaud G. J., Colomb M. G. Domain structure and associated functions of subcomponents C1r and C1s of the first component of human complement. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4477–4481. doi: 10.1073/pnas.82.13.4477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weiss V., Fauser C., Engel J. Functional model of subcomponent C1 of human complement. J Mol Biol. 1986 Jun 5;189(3):573–581. doi: 10.1016/0022-2836(86)90325-6. [DOI] [PubMed] [Google Scholar]
  34. Wilmot C. M., Thornton J. M. Analysis and prediction of the different types of beta-turn in proteins. J Mol Biol. 1988 Sep 5;203(1):221–232. doi: 10.1016/0022-2836(88)90103-9. [DOI] [PubMed] [Google Scholar]

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