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Optimal Length Transportation Hypothesis to Model Proteasome Product Size Distribution

Journal of Biological Physics volume 32, pages 231–243 (2006)Cite this article

Abstract

This paper discusses translocation features of the 20S proteasome in order to explain typical proteasome length distributions. We assume that the protein transport depends significantly on the fragment length with some optimal length which is transported most efficiently. By means of a simple one-channel model, we show that this hypothesis can explain both the one- and the three-peak length distributions found in experiments. A possible mechanism of such translocation is provided by so-called fluctuation-driven transport.

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References

  1. Coux, O., Tanaka, K., Goldberg, A.L.: Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65, 801–847 (1996)

    Article  Google Scholar 

  2. Kloetzel, P.M.: Antigen processing by the proteasome. Nat. Rev. Mol. Cell. Biol. 2, 179–187 (2001)

    Article  Google Scholar 

  3. Tamura, T., Nagy, I., Lupas, A., Lottspeich, F., Cejka, Z., Schoofs, G., Tanaka, K., De Mot, R., Baumeister, W.: The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus. Curr. Biol. 5, 766–774 (1995)

    Article  Google Scholar 

  4. Hendill, K.B.: The 19S multicatalytic ‘prosome’ proteinase is a constituitive enzyme in HeLa cells. Biochem. Int. 17, 471–478 (1988)

    Google Scholar 

  5. Kisselev, A.F., Akopian, T.N., Goldberg, A.L.: Range of sizes of peptide products generated during degradation of different proteins by archaeal proteasomes. J. Biol. Chem. 273, 1982–1989 (1998)

    Article  Google Scholar 

  6. Hilt, W., Wolf, D.H.: Proteasomes of the yeast S. cerevisiae: genes, structure and functions. Mol. Biol. Rep. 21, 3–10 (1995)

    Article  Google Scholar 

  7. Ciechanover, A.: The ubiquitin-proteasome proteolytic pathway. Cell 79, 13–21 (1994)

    Article  Google Scholar 

  8. Hochstrasser, M.: Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 30, 405–439 (1996)

    Article  Google Scholar 

  9. Goldberg, A.L., Cascio, P., Saric, T., Rock, K.L.: The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol. Immunol. 39, 147–164 (2002)

    Article  Google Scholar 

  10. Kloetzel, P.M.: Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat. Immunol. 5, 661–669 (2004a)

    Article  Google Scholar 

  11. Lankat-Buttgereit, B., Tampe, R.: The transporter associated with antigen processing: function and implications in human diseases. Physiol. Rev. 82, 187–204 (2002)

    Google Scholar 

  12. Rock, K.L., Goldberg, A.L.: Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu. Rev. Immunol. 17, 739–779 (1999)

    Article  Google Scholar 

  13. Shastri, N., Schwab, S.: Producing nature’s gene-chips: the generation of peptides for display by MHC class I molecules. Annu. Rev. Immunol. 20, 463–493 (2002)

    Article  Google Scholar 

  14. Adams, J., Palombella, V., Elliott, P.: Proteasome inhibition: a new strategy in cancer treatment. Invest. New Drugs 18, 109–121 (2000)

    Article  Google Scholar 

  15. Dou, Q.P., Smith, D., Daniel, K., Kazi, A.: Interruption of tumor cell cycle progression through proteasome inhibition: implications for cancer therapy. Prog. Cell Cycle Res. 5, 441–446 (2003)

    Google Scholar 

  16. Orlowski, R.Z.: The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ. 6, 303–313 (1999)

    Article  Google Scholar 

  17. Glickman, M., Ciechanover, A.: The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373–428 (2002)

    Google Scholar 

  18. Sakamoto, K.: Ubiquitin-dependent proteolysis: its role in human diseases and the design of therapeutic strategies. Mol. Genet. Metab. 77, 44–56 (2002)

    Article  Google Scholar 

  19. Zeng, B.Y., Medhurst, A.D., Jackson, M., Rose, S., Jenner, P.: Proteasomal activity in brain differs between species and brain regions and changes with age. Mech. Ageing Dev. 126, 760–766 (2005)

    Article  Google Scholar 

  20. Kloetzel, P.M.: The proteasome and MHC class I antigen processing. Biochem. Biophys. Acta. 1695, 225–233 (2004b)

    Article  Google Scholar 

  21. Rechsteiner, M., Realini, C., Ustrell, V.: The proteasome activator 11S REG (PA28) and class I antigen presentation. Biochem. J. 345, 1–15 (2000)

    Article  Google Scholar 

  22. Peters, J.M., Cejka, Z., Harris, J.R., Kleinschmidt, J.A., Baumeister, W.: Structural features of the 26S proteasome complex. J. Mol. Biol. 234, 932–937 (1993)

    Article  Google Scholar 

  23. Akopian, T.N., Kisselev, A.F., Goldberg, A.L.: Processive degradation of proteins and other catalytic properties of the proteasome from Thermoplasma acidophilum. J. Biol. Chem. 272, 1791–1798 (1997)

    Article  Google Scholar 

  24. Rapin, N., Kesmir, C., et al.: Integrating bioinformatics and systems biology for modelling of the immune system. J. Biol. Phys. (2006)

  25. Cascio, P., Hilton, C., Kisselev, A.F., Rock, K.L., Goldberg, A.L.: 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. EMBO J. 20, 2357–2366 (2001)

    Article  Google Scholar 

  26. Nussbaum, A.: From the test tube to the world wide web: the cleavage specificity of the proteasome. PhD thesis, Eberhard-Karls-Universitaet Tuebingen (2001)

  27. Nussbaum, A.K., Dick, T.P., Kielholz, W., Schirle, M., Stevanovic, S., Dietz, K., Heinemeyer, W., Groll, M., Wolf, D.H., Huber, R., Rammensee, H.G., Schild, H.: Cleavage motifs of the yeast 20S proteasome β subunits deduced form digests of enolase 1. Proc. Natl. Acad. Sci. USA 95, 12504–12509 (1998)

    Article  ADS  Google Scholar 

  28. Wenzel, T., Eckerskorn, C., Lottspeich, F., Baumeister, W.: Existence of a molecular ruler in proteasomes suggested by analysis of degradation products. FEBS Lett. 349, 205–209 (1994)

    Article  Google Scholar 

  29. Köhler, A., Cascio, P., Leggett, D.S., Woo, K.M., Goldberg, A.L., Finley, D.: The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product release. Mol. Cell (7), 1143–1152 (2001)

  30. Kuttler, C., Nussbaum, A.K., Dick, T.P., Rammensee, H.G., Schild, H., Hadeler, K.P.: An algorithm for the prediction of proteasomal cleavages. J. Mol. Biol. 298, 417–429 (2000)

    Article  Google Scholar 

  31. Kesmir, C., Nussbaum, A., Schild, H., Detours, V., Brunak, S.: Prediction of proteasome cleavage motifs by neural networks. Protein Eng. 15, 287–296 (2002)

    Article  Google Scholar 

  32. Tenzer, S., Peters, B., Bulik, S., Schoor, O., Lemmel, C., Schatz, M.M., Kloetzel, P.M., Rammensee, H.G., Schild, H., Holzhütter, H.G.: Modeling the MHC class I pathway by combining predictions of proteasomal clavage, TAP transport and MHC class I binding. CMLS, Cell. Mol. Life Sci. 62, 1025–1037 (2005)

    Article  Google Scholar 

  33. Schmidtke, G., Emch, S., Groettrup, M., Holzhuetter, H.G.: Evidence for the existence of a non-catalytic modifier site of peptide hydrolysis by the 20S proteasome. J. Biol. Chem. 275, 22056–22063 (2000)

    Article  Google Scholar 

  34. Stein, R.L., Melandri, F., Dick, L.: Kinetic characterization of the chymotrypic activity of the 20S proteasome. Biochemistry 35, 3899–3908 (1996)

    Article  Google Scholar 

  35. Stohwasser, R., Salzmann, U., Giesebrecht, J., Kloetzel, P.M., Holzhuetter, H.G.: Kinetic evidence for facilitation of peptide channelling by the proteasome activator PA28. Eur. J. Biochem. 267, 6221–6230 (2000)

    Article  Google Scholar 

  36. Holzhütter, H.G., Kloetzel, P.M.: A kinetic model of vertebrate 20S proteasome accounting for the generation of major proteolytic fragments from oligomeric peptide substrates. Biophys. J. 79, 1196–1205 (2000)

    Article  Google Scholar 

  37. Peters, B., Janek, K., Kuckelkorn, U., Holzhütter, H.G.: Assessment of proteasomal cleavage probabilities from kinetic analysis of time-dependent product formation. J. Mol. Biol. 318, 847–862 (2002)

    Article  Google Scholar 

  38. Gillespie, D.: A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. J. Comput. Phys. 22, 403–434 (1976)

    Article  ADS  MathSciNet  Google Scholar 

  39. Zaikin, A., Pöschel, T.: Peptide-size-dependent active transport in the proteasome. Europhys. Lett. 69, 725–731 (2005)

    Article  ADS  Google Scholar 

  40. Landa, P., Zaikin, A., Schimansky-Geier, L.: Effect of the potential shape and of a Brownian particle mass on noise-induced transport. Chaos, Solitons Fractals 12, 1459–1471 (2001)

    MATH  Article  Google Scholar 

  41. Brokaw, C.: Protein–protein ratchets: stochastic simulation and application to processive enzymes. Biophys. J. 81, 1333–1344 (2001)

    Google Scholar 

  42. Bier, M.: Processive motor protein as an overdamped brownian stepper. Phys. Rev. Lett. 91, 148104 (2003)

    Article  ADS  Google Scholar 

  43. Jung, P., Hänggi, P.: Resonantly driven Brownian motion: basic concepts and exact result. Phys. Rev. A 41, 2977 (1990)

    Article  ADS  MathSciNet  Google Scholar 

  44. Gaczynska, M., Osmulski, P.A., Gao, Y., Post, M.J., Simons, M.: Proline- and Arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity. Biochemistry 42, 8663–8670 (2003)

    Article  Google Scholar 

  45. Osmulski, P.A., Gaczynska, M.: Atomic force microscopy reveals two conformations of the 20S. J. Biol. Chem. 275, 13171–13174 (2000)

    Article  Google Scholar 

  46. Osmulski, P.A., Gaczynska, M.: Nonoenzymology of the 20S proteasome: proteasomal actiona are controlled by the allosteric transitions. Biochemistry 41, 7047–7053 (2002)

    Article  Google Scholar 

  47. Luciani, F., Kesmir, C., Mishto, M., Or-Guil, M., de Boer, R.J.: A mathematical model of protein degradation by the proteasome. Biophys. J. 88, 2422–2432 (2005)

    Article  Google Scholar 

  48. Dolenc, I., Seemüller, E., Baumeister, W.: Decelerated degradation of short peptides by the 20S proteasome. FEBS 434, 357–361 (1998)

    Article  Google Scholar 

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  1. Institute of Physics, University of Potsdam, D-14415, Potsdam, Germany

    Alexey Zaikin & Juergen Kurths

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  1. Alexey Zaikin
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  2. Juergen Kurths
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Correspondence to Alexey Zaikin.

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Zaikin, A., Kurths, J. Optimal Length Transportation Hypothesis to Model Proteasome Product Size Distribution. J Biol Phys 32, 231–243 (2006). https://doi.org/10.1007/s10867-006-9014-z

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  • DOI: https://doi.org/10.1007/s10867-006-9014-z

Key words

  • proteasome
  • protein translocation
  • stochastic process
  • ratchets