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. 1999 Jan;8(1):242–248. doi: 10.1110/ps.8.1.242

The insect immune protein scolexin is a novel serine proteinase homolog.

C M Finnerty 1, P A Karplus 1, R R Granados 1
PMCID: PMC2144095  PMID: 10210202

Abstract

Scolexin is a coagulation-provoking plasma protein induced in response to bacterial or viral infection of larval Manduca sexta, a large lepidopterous insect. Here we report the isolation and sequencing of two cDNA clones that code for scolexin isoforms sharing 80% sequence identity. The scolexin sequences have low but recognizable sequence similarity to members of the chymotrypsin family and represent a new subfamily of chymotrypsin-like serine proteinases. Comparison with known structures reveals the conservation of key catalytic residues and a possible specificity for small nonpolar residues. Most remarkable is the absence of a canonical activation peptide cleavage site. This suggests that the regulation of scolexin activity will involve a novel activation mechanism.

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Appel L. F., Prout M., Abu-Shumays R., Hammonds A., Garbe J. C., Fristrom D., Fristrom J. The Drosophila Stubble-stubbloid gene encodes an apparent transmembrane serine protease required for epithelial morphogenesis. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4937–4941. doi: 10.1073/pnas.90.11.4937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bairoch A., Bucher P., Hofmann K. The PROSITE database, its status in 1997. Nucleic Acids Res. 1997 Jan 1;25(1):217–221. doi: 10.1093/nar/25.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bentley D. R. Primary structure of human complement component C2. Homology to two unrelated protein families. Biochem J. 1986 Oct 15;239(2):339–345. doi: 10.1042/bj2390339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brenner S. The molecular evolution of genes and proteins: a tale of two serines. Nature. 1988 Aug 11;334(6182):528–530. doi: 10.1038/334528a0. [DOI] [PubMed] [Google Scholar]
  7. Chothia C., Lesk A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 Apr;5(4):823–826. doi: 10.1002/j.1460-2075.1986.tb04288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finnerty C. M., Granados R. R. The plasma protein scolexin from Manduca sexta is induced by baculovirus infection and other immune challenges. Insect Biochem Mol Biol. 1997 Jan;27(1):1–7. doi: 10.1016/s0965-1748(96)00075-6. [DOI] [PubMed] [Google Scholar]
  9. Freer S. T., Kraut J., Robertus J. D., Wright H. T., Xuong N. H. Chymotrypsinogen: 2.5-angstrom crystal structure, comparison with alpha-chymotrypsin, and implications for zymogen activation. Biochemistry. 1970 Apr 28;9(9):1997–2009. doi: 10.1021/bi00811a022. [DOI] [PubMed] [Google Scholar]
  10. Gardell S. J., Duong L. T., Diehl R. E., York J. D., Hare T. R., Register R. B., Jacobs J. W., Dixon R. A., Friedman P. A. Isolation, characterization, and cDNA cloning of a vampire bat salivary plasminogen activator. J Biol Chem. 1989 Oct 25;264(30):17947–17952. [PubMed] [Google Scholar]
  11. Greer J. Comparative model-building of the mammalian serine proteases. J Mol Biol. 1981 Dec 25;153(4):1027–1042. doi: 10.1016/0022-2836(81)90465-4. [DOI] [PubMed] [Google Scholar]
  12. Henikoff S., Henikoff J. G. Protein family classification based on searching a database of blocks. Genomics. 1994 Jan 1;19(1):97–107. doi: 10.1006/geno.1994.1018. [DOI] [PubMed] [Google Scholar]
  13. Horodyski F. M., Riddiford L. M., Truman J. W. Isolation and expression of the eclosion hormone gene from the tobacco hornworm, Manduca sexta. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8123–8127. doi: 10.1073/pnas.86.20.8123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hultmark D. Immune reactions in Drosophila and other insects: a model for innate immunity. Trends Genet. 1993 May;9(5):178–183. doi: 10.1016/0168-9525(93)90165-e. [DOI] [PubMed] [Google Scholar]
  15. Hultmark D., Steiner H., Rasmuson T., Boman H. G. Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia. Eur J Biochem. 1980 May;106(1):7–16. doi: 10.1111/j.1432-1033.1980.tb05991.x. [DOI] [PubMed] [Google Scholar]
  16. Iwanaga S. The limulus clotting reaction. Curr Opin Immunol. 1993 Feb;5(1):74–82. doi: 10.1016/0952-7915(93)90084-6. [DOI] [PubMed] [Google Scholar]
  17. Kyriakides T. R., McKillip J. L., Spence K. D. Biochemical characterization, developmental expression, and induction of the immune protein scolexin from Manduca sexta. Arch Insect Biochem Physiol. 1995;29(3):269–280. doi: 10.1002/arch.940290305. [DOI] [PubMed] [Google Scholar]
  18. Lerro K. A., Prestwich G. D. Cloning and sequencing of a cDNA for the hemolymph juvenile hormone binding protein of larval Manduca sexta. J Biol Chem. 1990 Nov 15;265(32):19800–19806. [PubMed] [Google Scholar]
  19. Li W., Riddiford L. M. Two distinct genes encode two major isoelectric forms of insecticyanin in the tobacco hornworm, Manduca sexta. Eur J Biochem. 1992 Apr 15;205(2):491–499. doi: 10.1111/j.1432-1033.1992.tb16805.x. [DOI] [PubMed] [Google Scholar]
  20. Ming Y. Z., Di X., Gomez-Sanchez E. P., Gomez-Sanchez C. E. Improved downward capillary transfer for blotting of DNA and RNA. Biotechniques. 1994 Jan;16(1):58–59. [PubMed] [Google Scholar]
  21. Minnick M. F., Rupp R. A., Spence K. D. A bacterial-induced lectin which triggers hemocyte coagulation in Manduca sexta. Biochem Biophys Res Commun. 1986 Jun 13;137(2):729–735. doi: 10.1016/0006-291x(86)91139-3. [DOI] [PubMed] [Google Scholar]
  22. Mole J. E., Anderson J. K., Davison E. A., Woods D. E. Complete primary structure for the zymogen of human complement factor B. J Biol Chem. 1984 Mar 25;259(6):3407–3412. [PubMed] [Google Scholar]
  23. Muta T., Miyata T., Misumi Y., Tokunaga F., Nakamura T., Toh Y., Ikehara Y., Iwanaga S. Limulus factor C. An endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like, and lectin-like domains. J Biol Chem. 1991 Apr 5;266(10):6554–6561. [PubMed] [Google Scholar]
  24. Navia M. A., McKeever B. M., Springer J. P., Lin T. Y., Williams H. R., Fluder E. M., Dorn C. P., Hoogsteen K. Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. Proc Natl Acad Sci U S A. 1989 Jan;86(1):7–11. doi: 10.1073/pnas.86.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rawlings N. D., Barrett A. J. Families of serine peptidases. Methods Enzymol. 1994;244:19–61. doi: 10.1016/0076-6879(94)44004-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rozwarski D. A., Gronenborn A. M., Clore G. M., Bazan J. F., Bohm A., Wlodawer A., Hatada M., Karplus P. A. Structural comparisons among the short-chain helical cytokines. Structure. 1994 Mar 15;2(3):159–173. doi: 10.1016/s0969-2126(00)00018-6. [DOI] [PubMed] [Google Scholar]
  27. Sato T., Endo Y., Matsushita M., Fujita T. Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein. Int Immunol. 1994 Apr;6(4):665–669. doi: 10.1093/intimm/6.4.665. [DOI] [PubMed] [Google Scholar]
  28. Schechter I., Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 1967 Apr 20;27(2):157–162. doi: 10.1016/s0006-291x(67)80055-x. [DOI] [PubMed] [Google Scholar]
  29. Sidén-Kiamos I., Skavdis G., Rubio J., Papaginnakis G., Louis C. Isolation and characterization of three serine protease genes in the mosquito Anopheles gambiae. Insect Mol Biol. 1996 Feb;5(1):61–71. doi: 10.1111/j.1365-2583.1996.tb00041.x. [DOI] [PubMed] [Google Scholar]
  30. Smith C. L., DeLotto R. A common domain within the proenzyme regions of the Drosophila snake and easter proteins and Tachypleus proclotting enzyme defines a new subfamily of serine proteases. Protein Sci. 1992 Sep;1(9):1225–1226. doi: 10.1002/pro.5560010915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thiel S., Vorup-Jensen T., Stover C. M., Schwaeble W., Laursen S. B., Poulsen K., Willis A. C., Eggleton P., Hansen S., Holmskov U. A second serine protease associated with mannan-binding lectin that activates complement. Nature. 1997 Apr 3;386(6624):506–510. doi: 10.1038/386506a0. [DOI] [PubMed] [Google Scholar]
  32. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Venot N., Sciaky M., Puigserver A., Desnuelle P., Laurent G. Amino acid sequence and disulfide bridges of subunit III, a defective endopeptidase present in the bovine pancreatic 6 S procarboxypeptidase A complex. Eur J Biochem. 1986 May 15;157(1):91–99. doi: 10.1111/j.1432-1033.1986.tb09642.x. [DOI] [PubMed] [Google Scholar]
  34. Volanakis J. E., Narayana S. V. Complement factor D, a novel serine protease. Protein Sci. 1996 Apr;5(4):553–564. doi: 10.1002/pro.5560050401. [DOI] [PMC free article] [PubMed] [Google Scholar]

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