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Structural Organization of Precursors of Thermolysin-like Proteinases

The Protein Journal volume 27, Article number: 343 (2008) Cite this article

Abstract

The primary structures of the full-length precursors of thermolysin-like proteinases (TLPs) were systemically analyzed. Structural comparison of the precursor amino-terminal regions (ATRs) removed during maturation allowed us to divide the family into two groups: peptidases with short (about 50 amino acids) and long (about 200 amino acids) ATRs. The accumulation of mutations in the ATRs of both types proved to correlate with that in the catalytic domains. No classical signal peptides were identified in the short ATRs, but they contained a conserved PPL-motif near the initiation methionine. The functional role of the short ATRs and PPL-motif is currently unclear. The C-terminal regions (CTRs) of TLP precursors, which are often removed during maturation, too, are found in about a half of precursors with long ATRs, but occur more rarely in precursors with short ATRs. CTRs in TLP precursors contain previously identified conserved domains typical for many other proteins and likely underlie the interaction with high molecular weight substrates.

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Notes

  1. The current MEROPS database (release 7.70) was supplemented by new M4 peptidase sequences. Each of these sequences was analyzed individually. The results of the analysis are summarized in the footnotes to Table 1.

Abbreviations

TLP:

Thermolysin-like proteinase

ATR:

Amino-terminal region

CTR:

Carboxy-terminal region

References

  1. Rawlings ND, Barrett AJ (1995) Methods Enzymol 248:183–228

    Article  CAS  Google Scholar 

  2. Rawlings ND, Morton FR, Barrett AJ (2006) Nucleic Acids Res 34:D270–272

    Article  CAS  Google Scholar 

  3. Matthews BW (1988) Acc Chem Res 21:333–340

    Article  CAS  Google Scholar 

  4. de Kreij A, Venema G, van den Burg B (2000) J Biol Chem 275:31115–31120

    Article  Google Scholar 

  5. Feder J (1967) Biochemistry 6:2088–2093

    Article  CAS  Google Scholar 

  6. Feder J, Schuck JM (1970) Biochemistry 9:2784–2791

    Article  CAS  Google Scholar 

  7. Schechter I, Berger A (1967) Biochem Biophys Res Commun 27:157–162

    Article  CAS  Google Scholar 

  8. Shinde U, Inouye M (2000) Semin Cell Dev Biol 11:35–44

    Article  CAS  Google Scholar 

  9. Braun P, Tommassen J, Filloux A (1996) Mol Microbiol 19:297–306

    Article  CAS  Google Scholar 

  10. Marie-Claire C, Ruffet E, Beaumont A, Roques BP (1999) J Mol Biol 285:1911–1915

    Article  CAS  Google Scholar 

  11. McIver KS, Kessler E, Olson JC, Ohman DE (1995) Mol Microbiol 18:877–889

    Article  CAS  Google Scholar 

  12. Tang B, Nirasawa S, Kitaoka M, Marie-Claire C, Hayashi K (2003) Biochem Biophys Res Commun 301:1093–1098

    Article  CAS  Google Scholar 

  13. Kessler E, Safrin M (1994) J Biol Chem 269:22726–22731

    CAS  Google Scholar 

  14. O’Donohue MJ, Roques BP, Beaumont A (1994) Biochem J 300(Pt 2):599–603

    CAS  Google Scholar 

  15. Serkina AV, Gorozhankina TF, Shevelev AB, Chestukhina GG (1999) FEBS Lett 456:215–219

    Article  CAS  Google Scholar 

  16. Wetmore DR, Wong SL, Roche RS (1992) Mol Microbiol 6:1593–1604

    Article  CAS  Google Scholar 

  17. Kearns DB, Bonner PJ, Smith DR, Shimkets LJ (2002) J Bacteriol 184:1678–1684

    Article  CAS  Google Scholar 

  18. Miyamoto K, Nukui E, Hirose M, Nagai F, Sato T, Inamori Y, Tsujibo H (2002) Appl Environ Microbiol 68:5563–5570

    CAS  Google Scholar 

  19. Miyamoto K, Tsujibo H, Nukui E, Itoh H, Kaidzu Y, Inamori Y (2002) Biosci Biotechnol Biochem 66:416–421

    Article  CAS  Google Scholar 

  20. Miyoshi S, Kawata K, Tomochika K, Shinoda S, Yamamoto S (2001) Toxicon 39:1883–1886

    Article  CAS  Google Scholar 

  21. Miyoshi S, Wakae H, Tomochika K, Shinoda S (1997) J Bacteriol 179:7606–7609

    CAS  Google Scholar 

  22. Demidyuk IV, Kalashnikov AE, Gromova TY, Gasanov EV, Safina DR, Zabolotskaya MV, Rudenskaya GN, Kostrov SV (2006) Protein Expr Purif 47:551–561

    Article  CAS  Google Scholar 

  23. Zabolotskaya MV, Demidyuk IV, Akimkina TV, Kostrov SV (2004) Protein J 23:483–492

    Article  CAS  Google Scholar 

  24. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) Nucleic Acids Res 25:4876–4882

    Article  CAS  Google Scholar 

  25. Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) J Mol Biol 340:783–795

    Article  CAS  Google Scholar 

  26. Schneider TD, Stephens RM (1990) Nucleic Acids Res 18:6097–6100

    Article  CAS  Google Scholar 

  27. Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) Genome Res 14:1188–1190

    Article  CAS  Google Scholar 

  28. Felsenstein J (2005) PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author. Department of Genome Sciences, University of Washington, Seattle

    Google Scholar 

  29. O’Donohue MJ, Beaumont A (1996) J Biol Chem 271:26477–26481

    Article  CAS  Google Scholar 

  30. Tang B, Nirasawa S, Kitaoka M, Hayashi K (2002) Biochim Biophys Acta 1596:16–27

    CAS  Google Scholar 

  31. Tang B, Nirasawa S, Kitaoka M, Hayashi K (2002) Biochem Biophys Res Commun 296:78–84

    Article  CAS  Google Scholar 

  32. Mansfeld J, Petermann E, Durrschmidt P, Ulbrich-Hofmann R (2005) Protein Expr Purif 39:219–228

    Article  CAS  Google Scholar 

  33. Braun P, Bitter W, Tommassen J (2000) Microbiology 146(Pt 10):2565–2572

    CAS  Google Scholar 

  34. Marie-Claire C, Roques BP, Beaumont A (1998) J Biol Chem 273:5697–5701

    Article  CAS  Google Scholar 

  35. McIver K, Kessler E, Ohman DE (1991) J Bacteriol 173:7781–7789

    CAS  Google Scholar 

  36. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL, Studholme DJ, Yeats C, Eddy SR (2004) Nucleic Acids Res 32:D138–141

    Article  CAS  Google Scholar 

  37. McIver KS, Kessler E, Ohman DE (2004) Microbiology 150:3969–3977

    Article  CAS  Google Scholar 

  38. Yeats C, Rawlings ND, Bateman A (2004) Trends Biochem Sci 29:169–172

    Article  CAS  Google Scholar 

  39. Kyostio SR, Cramer CL, Lacy GH (1991) J Bacteriol 173:6537–6546

    CAS  Google Scholar 

  40. Kwon YT, Lee HH, Rho HM (1993) Gene 125:75–80

    Article  CAS  Google Scholar 

  41. Novikova SI, Serkina AV, Konstantinova GE, Khlebalina OI, Chestukhina GG, Shevelev AB (2001) Vopr Med Khim 47:123–131

    CAS  Google Scholar 

  42. Shinde U, Fu X, Inouye M (1999) J Biol Chem 274:15615–15621

    Article  CAS  Google Scholar 

  43. Shinde UP, Liu JJ, Inouye M (1997) Nature 389:520–522

    Article  CAS  Google Scholar 

  44. Yasuda Y, Tsukuba T, Okamoto K, Kadowaki T, Yamamoto K (2005) J Biochem (Tokyo) 138:621–630

    CAS  Google Scholar 

  45. Hase CC, Finkelstein RA (1990) Infect Immun 58:4011–4015

    CAS  Google Scholar 

  46. Kato JY, Suzuki A, Yamazaki H, Ohnishi Y, Horinouchi S (2002) J Bacteriol 184:6016–6025

    Article  CAS  Google Scholar 

  47. Lee SO, Kato J, Nakashima K, Kuroda A, Ikeda T, Takiguchi N, Ohtake H (2002) Biosci Biotechnol Biochem 66:1366–1369

    Article  CAS  Google Scholar 

  48. Nirasawa S, Nakajima Y, Zhang ZZ, Yoshida M, Hayashi K (1999) Biochem J 341(Pt 1):25–31

    Article  CAS  Google Scholar 

  49. Norqvist A, Norrman B, Wolf-Watz H (1990) Infect Immun 58:3731–3736

    CAS  Google Scholar 

  50. Oda K, Okayama K, Okutomi K, Shimada M, Sato R, Takahashi S (1996) Biosci Biotechnol Biochem 60:463–467

    CAS  Article  Google Scholar 

  51. Chuang YC, Chang TM, Chang MC (1997) Gene 189:163–168

    Article  CAS  Google Scholar 

  52. Miyoshi N, Shimizu C, Miyoshi S, Shinoda S (1987) Microbiol Immunol 31:13–25

    CAS  Google Scholar 

  53. Miyoshi S, Sonoda Y, Wakiyama H, Rahman MM, Tomochika K, Shinoda S, Yamamoto S, Tobe K (2002) Microb Pathog 33:127–134

    Article  CAS  Google Scholar 

  54. David VA, Deutch AH, Sloma A, Pawlyk D, Ally A, Durham DR (1992) Gene 112:107–112

    Article  CAS  Google Scholar 

  55. Teo JW, Zhang LH, Poh CL (2003) Gene 303:147–156

    Article  CAS  Google Scholar 

  56. Behmlander RM, Dworkin M (1994) J Bacteriol 176:6295–6303

    CAS  Google Scholar 

  57. Matsushita O, Koide T, Kobayashi R, Nagata K, Okabe A (2001) J Biol Chem 276:8761–8770

    Article  CAS  Google Scholar 

  58. Toyoshima T, Matsushita O, Minami J, Nishi N, Okabe A, Itano T (2001) Connect Tissue Res 42:281–290

    Article  CAS  Google Scholar 

  59. Creemers JW, Siezen RJ, Roebroek AJ, Ayoubi TA, Huylebroeck D, Van de Ven WJ (1993) J Biol Chem 268:21826–21834

    CAS  Google Scholar 

  60. Gluschankof P, Fuller RS (1994) EMBO J 13:2280–2288

    CAS  Google Scholar 

  61. Rovere C, Luis J, Lissitzky JC, Basak A, Marvaldi J, Chretien M, Seidah NG (1999) J Biol Chem 274:12461–12467

    Article  CAS  Google Scholar 

  62. Creemers JW, Usac EF, Bright NA, Van de Loo JW, Jansen E, Van de Ven WJ, Hutton JC (1996) J Biol Chem 271:25284–25291

    Article  CAS  Google Scholar 

  63. Lusson J, Benjannet S, Hamelin J, Savaria D, Chretien M, Seidah NG (1997) Biochem J 326(Pt 3):737–744

    CAS  Google Scholar 

  64. Taylor NA, Shennan KI, Cutler DF, Docherty K (1997) Biochem J 321(Pt 2):367–373

    CAS  Google Scholar 

  65. Ueda K, Lipkind GM, Zhou A, Zhu X, Kuznetsov A, Philipson L, Gardner P, Zhang C, Steiner DF (2003) Proc Natl Acad Sci USA 100:5622–5627

    Article  CAS  Google Scholar 

  66. Zhou A, Martin S, Lipkind G, LaMendola J, Steiner DF (1998) J Biol Chem 273:11107–11114

    Article  CAS  Google Scholar 

  67. Zhu X, Muller L, Mains RE, Lindberg I (1998) J Biol Chem 273:1158–1164

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Russian Foundation for Basic Research (project nos. 06-04-48678, 06-04-48690, and 06-04-08123).

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Affiliations

  1. Laboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov sq. 2, Moscow, 123182, Russia

    Ilya V. Demidyuk, Eugene V. Gasanov, Dina R. Safina & Sergey V. Kostrov

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  1. Ilya V. Demidyuk
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  2. Eugene V. Gasanov
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  3. Dina R. Safina
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  4. Sergey V. Kostrov
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Correspondence to Ilya V. Demidyuk.

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Demidyuk, I.V., Gasanov, E.V., Safina, D.R. et al. Structural Organization of Precursors of Thermolysin-like Proteinases. Protein J 27, 343 (2008). https://doi.org/10.1007/s10930-008-9143-2

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  • DOI: https://doi.org/10.1007/s10930-008-9143-2

Keywords

  • Classification
  • Propeptide
  • Protein motif
  • Protein precursor
  • Thermolysin-like proteinase