Synthesis and structural characterization of a mimetic membrane-anchored prion protein

The FEBS Journal
Matthew R HicksTeresa J T Pinheiro

Abstract

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrP(Sc)) of the host encoded prion protein (PrP(C)) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrP(C) and PrP(Sc) have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrP(C) to PrP(Sc), but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatid...Continue Reading

References

Jan 1, 1977·Methods in Enzymology·G L Kenyon, T W Bruice
Apr 1, 1985·Cell·B OeschL E Hood
Sep 1, 1988·European Journal of Biochemistry·E TurkS B Prusiner
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M PanF E Cohen
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·M VeyS B Prusiner
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·K KanekoS B Prusiner
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·T L JamesF E Cohen
Dec 31, 1997·Nature·P Brown
May 20, 1998·Cell·S B PrusinerF E Cohen
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·J H VilesH J Dyson
Jul 10, 1999·Clinical Microbiology Reviews·D A Harris
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·R ZahnK Wüthrich
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·H MoH J Dyson
Apr 13, 2001·Biochemistry·P M RuddR A Dwek
Jul 13, 2001·Advances in Protein Chemistry·K Wüthrich, R Riek
Feb 6, 2002·Journal of Molecular Biology·Narinder Sanghera, Teresa J T Pinheiro
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Holger WilleStanley B Prusiner
Mar 26, 2003·The Journal of General Virology·Louise KirbyJames Hope
Jun 5, 2003·Biochemistry·Colin S BurnsGlenn L Millhauser
Jul 11, 2003·The EMBO Journal·Claire SunyachRoger Morris
Nov 13, 2003·Methods in Enzymology·Olivier Nosjean, Bernard Roux
Nov 13, 2003·Methods in Enzymology·Barbara MuiMichael J Hope
Dec 31, 2003·Biochemical and Biophysical Research Communications·Peter CritchleyTeresa J T Pinheiro
Mar 20, 2004·The Journal of Biological Chemistry·Heike EberlRudi Glockshuber
Mar 24, 2004·Journal of Molecular Biology·L F HaireP M Bayley
May 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Cédric GovaertsFred E Cohen
Jul 2, 2004·Molecular Biology of the Cell·Daniela SarnataroChiara Zurzolo
Aug 3, 2004·Science·Giuseppe LegnameStanley B Prusiner
Nov 3, 2004·Biochimica Et Biophysica Acta·Annela M SeddonPaula J Booth

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Citations

Aug 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kerstin ElfrinkKlaus Gerwert
Feb 24, 2009·Annual Review of Biochemistry·Byron CaugheyMartin Jeffrey
Jan 12, 2007·Biological Chemistry·Kerstin ElfrinkDetlev Riesner
Oct 11, 2011·Cellular and Molecular Life Sciences : CMLS·Rafael LindenLuis Mauricio T R Lima
Feb 10, 2007·The FEBS Journal·Ilia V Baskakov
Sep 24, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Nam Ky ChuChristian F W Becker
Sep 22, 2007·Chemistry & Biology·Diana OlschewskiChristian F W Becker
Feb 13, 2014·The Journal of Physical Chemistry. B·Kaoru NomuraKeiko Shimamoto
Apr 22, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Lei ShiYan-Mei Li
Nov 17, 2016·Journal of Virology·Karen E MarshallGerald S Baron
Jun 20, 2008·Molecular BioSystems·Diana Olschewski, Christian F W Becker
Sep 25, 2008·Angewandte Chemie·Christian F W BeckerPeter H Seeberger
Feb 10, 2010·Chembiochem : a European Journal of Chemical Biology·Yug Varma, Tamara Hendrickson
Apr 9, 2008·Physiological Reviews·Rafael LindenRicardo R Brentani
Nov 13, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Stefanie Hackl, Christian F W Becker
Sep 14, 2014·The Journal of Biological Chemistry·Nam K ChuChristian F W Becker
Nov 8, 2008·Journal of the American Chemical Society·John M AntosHidde L Ploegh
Jun 19, 2008·Biochemistry·Margot G Paulick, Carolyn R Bertozzi
Aug 25, 2007·Journal of the American Chemical Society·Margot G PaulickCarolyn R Bertozzi

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