Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids.

Proceedings of the National Academy of Sciences of the United States of America
Nathan R DeleaultSurachai Supattapone

Abstract

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of purified recombinant (rec)PrP substrate into infectious recPrP(Sc) molecules. Other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate recPrP(Sc) formation in the absence of RNA. PE facilitated the propagation of PrP(Sc) molecules derived from all four different animal species tested including mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP(Sc) formation in vitro. Phospholipase treatment abolished the ability of brain...Continue Reading

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Citations

Jun 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nathan R DeleaultSurachai Supattapone
Aug 30, 2012·The Journal of Biological Chemistry·Helen M J KlemmVictoria A Lawson
Jul 19, 2012·The Journal of Biological Chemistry·Natallia MakaravaIlia V Baskakov
Sep 13, 2012·The Journal of Biological Chemistry·Mikhail Bogdanov, William Dowhan
Nov 22, 2012·The Journal of Biological Chemistry·Natallia MakaravaIlia V Baskakov
Nov 28, 2013·The Journal of Biological Chemistry·Huanhuan L CuiAndrew F Hill
Sep 1, 2012·Journal of Biomolecular Structure & Dynamics·Xiaojing CongGiuseppe Legname
Feb 6, 2013·PLoS Pathogens·Glenn C Telling
Apr 5, 2014·PLoS Pathogens·Joel C WattsStanley B Prusiner
Jan 29, 2013·International Journal of Molecular Sciences·Zvezdan Pavlovic, Marica Bakovic
Dec 18, 2013·Biochemistry·Ashley A ZurawelSurachai Supattapone
Jan 17, 2014·The Journal of Clinical Investigation·Charles E MaysJiri G Safar
Nov 14, 2013·International Journal of Cell Biology·Isabelle Acquatella-Tran Van BaVéronique Perrier
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Heidi VitracWilliam Dowhan
Jul 31, 2013·FEBS Letters·Arpana DuttaWitold K Surewicz
Jan 16, 2016·International Journal of Molecular Sciences·Abigail B DiackJean C Manson
Jan 27, 2016·Translational Psychiatry·N VoyleUNKNOWN Alzheimer's Disease Neuroimaging Initiative
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Jul 16, 2015·Biochemistry·Paul D DinkelMartin Margittai
Apr 17, 2013·Brain Pathology·Hans Kretzschmar, Jörg Tatzelt
Jun 23, 2015·Annals of Neurology·Joel C WattsStanley B Prusiner
Oct 2, 2014·Protein Science : a Publication of the Protein Society·Alakesh Bera, Pradip K Nandi
Jan 24, 2014·International Journal of Cell Biology·Ilaria PoggioliniPiero Parchi
Sep 27, 2012·Biochimica Et Biophysica Acta·Luce Farine, Peter Bütikofer
Dec 3, 2014·Virus Research·Paula Saá, Larisa Cervenakova
Dec 3, 2014·Virus Research·Nhat Tran Thanh LeGiuseppe Legname
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May 14, 2014·Prion·Fozia SaleemDavid S Wishart
Oct 15, 2013·Structure·Michael B MillerSurachai Supattapone

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