The mechanism of prion inhibition by HET-S.

Molecular Cell
Jason GreenwaldRoland Riek

Abstract

HET-S (97% identical to HET-s) has an N-terminal globular domain that exerts a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation. We show that HET-S fails to form fibrils in vitro and that it inhibits HET-s PFD fibrillization in trans. In vivo analyses indicate that beta-structuring of the HET-S PFD is required for HET-S activity. The crystal structures of the globular domains of HET-s and HET-S are highly similar, comprising a helical fold, while NMR-based characterizations revealed no differences in the conformations of the PFDs. We conclude that prion inhibition is not encoded by structure but rather in stability and oligomerization properties: when HET-S forms a prion seed or is incorporated into a HET-s fibril via its PFD, the beta-structuring in this domain induces a change in its globular domain, generating a molecular species that is incompetent for fibril growth.

References

Dec 1, 1993·Protein Science : a Publication of the Protein Society·L Swint, A D Robertson
Apr 1, 1997·Nature Structural Biology·K Diederichs, P A Karplus
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·V CoustouJ Begueret
May 18, 1999·Molecular and Cellular Biology·M L Maddelein, R B Wickner
Jul 6, 2000·The EMBO Journal·E Fernandez-BellotC Cullin
Sep 7, 2000·Microbiology and Molecular Biology Reviews : MMBR·S J Saupe
Mar 12, 2002·Molecular Microbiology·V Coustou-LinaresS J Saupe
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Elizabeth PottertonMartin Noble
Dec 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jia-Jia LiuSusan L Lindquist
Apr 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Henk J P DalstraRolf F Hoekstra
Sep 14, 2004·Nature Biotechnology·Ana-Maria Fernandez-EscamillaLuis Serrano
Jun 10, 2005·Nature·Christiane RitterRoland Riek
Feb 17, 2006·Neurobiology of Aging·Charles G Glabe
Jul 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Martin L DuennwaldSusan Lindquist
Sep 16, 2006·The Journal of Biological Chemistry·Benjamin Dehay, Anne Bertolotti
Apr 26, 2007·Protein Science : a Publication of the Protein Society·Shahin ZibaeeLouise C Serpell
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Aug 28, 2007·Protein Engineering, Design & Selection : PEDS·Antonio TrovatoSilvio C E Tosatto
Feb 1, 2008·Annual Review of Pathology·Adriano AguzziMathias Heikenwaelder
Sep 19, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Reed B WicknerHerman K Edskes
Aug 18, 2009·The FEBS Journal·R SabatéS Ventura
Sep 15, 2009·Journal of Molecular Biology·Christian WasmerBeat H Meier

❮ Previous
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Citations

Sep 27, 2012·Journal of Medicinal Chemistry·Laura C LópezJavier Sancho
Nov 18, 2010·Nature Reviews. Molecular Cell Biology·Mick F Tuite, Tricia R Serio
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Naoko MizunoAlasdair C Steven
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jacques-Philippe ColletierDavid Eisenberg
Jun 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alfons J M DebetsSven J Saupe
Nov 28, 2013·Annual Review of Genetics·Stanley B Prusiner
Jan 10, 2013·PLoS Biology·Carolin SeuringRoland Riek
Jan 10, 2013·PLoS Biology·Douglas M Fowler, Jeffery W Kelly
Jun 2, 2012·PLoS Pathogens·Sven J Saupe, Asen Daskalov
Nov 16, 2014·Genome Biology and Evolution·Witold DyrkaSven J Saupe
Feb 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Asen DaskalovSven J Saupe
Feb 22, 2011·Seminars in Cell & Developmental Biology·Sven J Saupe
Jul 30, 2015·Scientific Reports·Asen DaskalovSven J Saupe
Aug 19, 2015·Progress in Nuclear Magnetic Resonance Spectroscopy·Theodoros K KaramanosSheena E Radford
Sep 28, 2012·The Biochemical Journal·Michael LandrehHans Jörnvall
May 17, 2014·Prion·Raimon Sabate
Oct 16, 2010·Structure·Jason Greenwald, Roland Riek
Jan 2, 2014·Fungal Genetics and Biology : FG & B·M A Van der NestJ Stenlid
May 6, 2016·Frontiers in Molecular Neuroscience·Alba EspargaróRaimon Sabate
Jul 2, 2014·Molecular Cell·Theodoros K KaramanosSheena E Radford
May 8, 2018·Pathogens·José Miguel Flores-FernándezHolger Wille
Apr 17, 2013·G3 : Genes - Genomes - Genetics·Frédérique BidardSven J Saupe
Jul 26, 2019·PLoS Genetics·Cristina A BarraganEunyoung Chae
May 16, 2019·Cold Spring Harbor Perspectives in Biology·Daniel Otzen, Roland Riek
Jul 22, 2020·Annual Review of Microbiology·Sven J Saupe
Jul 22, 2020·Annual Review of Microbiology·A Pedro GonçalvesN Louise Glass
Apr 14, 2017·Biomolecules·Antoine Loquet, Sven J Saupe
Sep 5, 2020·International Journal of Molecular Sciences·Yanhong PangSuparna Sanyal
Jun 30, 2016·Cold Spring Harbor Perspectives in Biology·Roland Riek, Sven J Saupe
Sep 25, 2020·The New Phytologist·Wei-Lin WanEunyoung Chae
Dec 10, 2020·Nature Reviews. Immunology·Isabel M L SaurPaul Schulze-Lefert
Jan 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Asen DaskalovAntoine Loquet
Feb 13, 2021·Prion·Asen Daskalov, Sven J Saupe
Jul 19, 2018·Journal of Molecular Biology·Maya DeshmukhMatthew R Chapman
Jan 21, 2019·Biochemical Pharmacology·Madhura KulkarniJ Marie Hardwick
Jun 20, 2020·Current Opinion in Plant Biology·Joanna M FeehanJonathan Dg Jones
Oct 16, 2020·Journal of Molecular Biology·Witold DyrkaSven J Saupe

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