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2003 | 08 | 2 |

Tytuł artykułu

The prion peptide forms ion channels in planar lipid bilayers

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
One of the hypotheses concerning the pathogenic properties of the prion protein, considers its influence on cellular ion homeostasis. Using the lipid bilayer technique, the influence of prion-derived peptides on the lipid bilayer conductance was characterized. To evaluate the physiological significance and possible pathological functions of the peptides, their effect on the membrane potential and respiration rate of hippocampal mitochondria was also studied. We used a peptide bearing the human prion protein sequence YSNQNNF (PrP [169- 175]), and peptide SSQNNF (PrP [170-175]) bearing a naturally-occurring mutation in position 171 [N→S] linked to schizoaffective diseases in humans (Samaia, H.B., Mari, J.J., Vallada, H.P., Moura R.P., Simpson A.J.G., Brentani R.R. A prion-linked psychiatric disorder. Nature 390 (1997) 241). In this report, we show that PrP [170-175] N171S increases the conductance of planar lipid bilayers. Based on the conductance of single channel currents recorded in 500/500 mM KCl (cis/trans), we found a single channel conductance of 8 to 26 pS. The native prion peptide PrP [169-175] does not form ion channels in the lipid bilayer. Neither of the peptides significantly changed the membrane potential or respiration rate of isolated rat hippocampal mitochondria. We propose a possible mechanism for channel formation by aggregation of the prion-derived peptide.

Wydawca

-

Rocznik

Tom

08

Numer

2

Opis fizyczny

p.353-362,fig.

Twórcy

autor
  • Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland
autor
autor
autor
autor
autor

Bibliografia

  • 1.Prusiner, S.B., Scott, M.R., DeArmond, S.J. and Cohen, F.E. Prion protein biology. Cell 93 (1998) 337-348.
  • 2.Prusiner, S.B. Prions. Proc. Nat. Acad. Sci. USA 95 (1998) 13363-13383.
  • 3.Brown, D.R. and Besinger, A. Prion protein expression and superoxide dismutase activity Biochem. J. 334 (1998) 423-426.
  • 4.Brown, D.R., Clive, C. and Haswell S.J. Antioxidant activity related to copper binding of native prion protein. J. Neurochem. 76 (2001) 69-76.
  • 5.Kramer, M.L., Kratzin, H.D., Schmidt, B., Romer, A., Windl, O., Liemann, S., Hornemann, S. and Kretzschmar, H. Prion protein binds copper within the physiological concentration range. J. Biol.Chem. 276 (2001) 16711- 16719.
  • 6.Chapron, Y., Peyrin, J-M., Crouzy, S., Jaegly, A. and Dormont, D. Theoretical analysis of the implication of PrP in neuronal death during transmissible subacute spongiform encephalopathies: hypothesis of a PrP oligomeric channel. J. Theor. Biol.. 204 (2000) 103-111.
  • 7.Kourie, J.I. and Culverson, A. Prion peptide fragment PrP[106-126] forms distinct cation channel types. J. Neurosci. Res. 62 (2000) 120-133.
  • 8.Chiesa, R. and Harris, D.A. Prion diseases: what is a neurotoxic molecule. Neurobiol. Dis. 8 (2001) 743-763.
  • 9.Kourie, J.I. Prion channel proteins and their role in vacuolation and neurodegenerative diseases. Eur. Biophys. J. 31 (2002) 409-416.
  • 10.Florio, T., Grimaldi, M., Scorziello, A., Salmona, M., Bugiani, O., Tagliavini, F., Forloni, G. and Schettini, G. Intracellular calcium rise through L-type calcium channels, as molecular mechanism for the prion protein fragment 106-126 induced astrioglial proliferation. Biochem. Biophys. Res Commun. 228 (1996) 397-405.
  • 11.Come, J.H., Fraser, P.E. and Lansbury, P.T.Jr. A kinetic model for amyloid formation in the prion disesases: importance of seeding. Proc. Natl. Acad. Sci. USA 90 (1993) 5959-5963.
  • 12.Jarret, J.T. and Lansbury, P.T.Jr. Seeding „one dimensional crystallization“ of amyloid: A pathogenic mechanism in Alzheimers disease and scrapie. Cell 73 (1993) 1055-1058.
  • 13.Sondheimer, N. and Lindquist, S. Rnq l: an epigenetic modifier of protein function in yeast. Mol. Cell. 5 (2000) 163-172.
  • 14.Balbirnie, M., Grothe, R. and Eisenberg, D.S. An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta-sheet structure for amyloid. Proc. Nat. Acad. Sci. USA 98 (2001) 2375-2380.
  • 15.Rost, B. and Sander, C. Prediction of protein secondary structure at better than 70% accuracy. J. Mol. Biol. 232 (1993) 584-599.
  • 16.Zahn, R., Liu, A., Riek, R., Von Schroetter, C., Garcia, F.L., Billeter, M., Calzolai, L., Wider, G. and Wutrich, K. NMR solution structure of the human prion protein. Proc. Nat. Acad. Sci. USA 97 (2000) 145-150.
  • 17.O’Donovan, C.N., Tobin, D. and Cotter, T.G. Prion protein fragment PrP(106-126) induces apoptosis via mitochondrial disruption in neuronal SH-SY5Y cells. J. Biol. Chem. 276 (2001) 43516-43523.

Typ dokumentu

Bibliografia

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