The two-stage pathway of ataxin-3 fibrillogenesis involves a polyglutamine-independent step.

The Journal of Biological Chemistry
Andrew M EllisdonStephen P Bottomley

Abstract

The aggregation of ataxin-3 is associated with spinocerebellar ataxia type 3, which is characterized by the formation of intraneuronal aggregates. However, the mechanism of aggregation is currently not well understood. Ataxin-3 consists of a folded Josephin domain followed by two ubiquitin-interacting motifs and a C-terminal polyglutamine tract, which in the non-pathological form is less than 45 residues in length. We demonstrate that ataxin-3 with 64 glutamines (at(Q64)) undergoes a two-stage aggregation. The first stage involves formation of SDS-soluble aggregates, and the second stage results in formation of SDS-insoluble aggregates via the poly(Q) region. Both these first and second stage aggregates display typical amyloid-like characteristics. Under the same conditions at(Q15) and at(QHQ) undergo a single step aggregation event resulting in SDS-soluble aggregates, which does not involve the polyglutamine tract. These aggregates do not convert to the SDS-insoluble form. These observations demonstrate that ataxin-3 has an inherent capacity to aggregate through its non-polyglutamine domains. However, the presence of a pathological length polyglutamine tract introduces an additional step resulting in formation of a highly stab...Continue Reading

References

Jul 12, 1997·Lancet·R W Carrell, D A Lomas
Aug 29, 1997·The Journal of Biological Chemistry·D M WalshD B Teplow
Aug 1, 1997·Neuroscience Research·J GotoI Kanazawa
Nov 20, 1998·Trends in Genetics : TIG·A Kakizuka
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·E ScherzingerE E Wanker
Aug 28, 1999·The Journal of Biological Chemistry·D M WalshD B Teplow
Oct 3, 1999·Methods in Enzymology·F Ferrone
Jun 9, 2000·Annual Review of Neuroscience·H Y Zoghbi, H T Orr
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·A E Bevivino, P J Loll
Nov 2, 2001·Trends in Molecular Medicine·R L Margolis, C A Ross
Jun 5, 2002·Biochemistry·Songming ChenRonald Wetzel
Jul 24, 2002·European Journal of Biochemistry·Eva Zerovnik
Aug 13, 2002·The Journal of Biological Chemistry·Michelle A PoirierChristopher A Ross
Aug 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Songming ChenRonald Wetzel
Oct 24, 2002·Human Molecular Genetics·Wen YangRonald Wetzel
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christopher A RossMario Amzel
Jul 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kathryn M DonaldsonClaudio A P Joazeiro
Aug 28, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Massimo Stefani, Christopher M Dobson
Aug 29, 2003·Human Molecular Genetics·Hartmut ScheelKay Hofmann
Feb 18, 2004·Current Medicinal Chemistry·Michelle K M ChowStephen P Bottomley
Jun 10, 2004·IUBMB Life·Andrew M Ellisdon, Stephen P Bottomley
Aug 25, 2004·Biochemical and Biophysical Research Communications·Michelle K M ChowStephen P Bottomley
Sep 4, 2004·The Journal of Biological Chemistry·Michelle K M ChowStephen P Bottomley
Sep 24, 2004·PLoS Biology·Sean R CollinsJonathan S Weissman
Oct 1, 2004·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Quasar Saleem PadiathSamir Kumar Brahmachari

❮ Previous
Next ❯

Citations

Jun 2, 2010·Acta Neuropathologica·Sarah L Hands, Andreas Wyttenbach
Mar 9, 2011·Journal of the American Chemical Society·V N SivanandamPatrick C A van der Wel
Jul 10, 2012·The Journal of Physical Chemistry. B·Markus S MiettinenZoya Ignatova
Mar 10, 2009·Nature Structural & Molecular Biology·Ashwani K ThakurRonald Wetzel
Feb 15, 2011·Nature Structural & Molecular Biology·Karunakar KarRonald Wetzel
Sep 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Angel OrteDavid Klenerman
May 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Amy L RobertsonStephen P Bottomley
Oct 19, 2007·The Journal of Biological Chemistry·Zoya IgnatovaLila M Gierasch
Nov 10, 2010·Nucleic Acids Research·Amy L RobertsonAshley M Buckle
Jul 11, 2009·Protein Engineering, Design & Selection : PEDS·Helen M Saunders, Stephen P Bottomley
Sep 3, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura MasinoAnnalisa Pastore
Jan 7, 2011·PloS One·Patrick Lajoie, Erik Lee Snapp
Sep 13, 2012·PloS One·Mário N LaçoA Cristina Rego
Jul 31, 2013·PloS One·Helen M SaundersStephen P Bottomley
May 13, 2014·PloS One·Nakeirah T M ChristieElise A Kikis
Nov 19, 2013·Cell Biochemistry and Biophysics·Eamonn F HealyPeter J King
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Lauren E BuchananMartin T Zanni
Oct 18, 2014·Nature Chemical Biology·Anne GershensonSheena E Radford
Dec 3, 2014·Computational Biology and Chemistry·Vandna Sharma, Kalyan Sundar Ghosh
Jul 4, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Iwona StawoskaGrazyna Stochel
Feb 18, 2016·The Journal of Cell Biology·Carlos A MatosAna Luísa Carvalho
Jan 29, 2013·Journal of Molecular Biology·Karunakar KarRonald Wetzel
Jun 21, 2012·The International Journal of Biochemistry & Cell Biology·Gaetano InvernizziSalvador Ventura
Feb 7, 2012·Journal of Molecular Biology·Ronald Wetzel
Sep 29, 2011·Journal of Molecular Biology·Amy L RobertsonStephen P Bottomley
Jul 12, 2011·Progress in Neurobiology·Carlos A MatosAna Luísa Carvalho
Dec 1, 2009·Journal of Molecular Biology·Anja S KnauppStephen P Bottomley
Jun 6, 2014·Chemical Reviews·Francois-Xavier TheilletPhilipp Selenko
Nov 17, 2015·Nature Structural & Molecular Biology·Saskia PollingDanny M Hatters
Apr 17, 2007·Biochemical and Biophysical Research Communications·Erkang FeiGuanghui Wang
Mar 17, 2007·Journal of Molecular Biology·Andrew M EllisdonStephen P Bottomley
Feb 16, 2007·The International Journal of Biochemistry & Cell Biology·Fernanda RicchelliPaolo Zatta
Dec 19, 2006·Journal of Molecular Biology·Glenn A PowersStephen P Bottomley
Aug 13, 2015·Protein Science : a Publication of the Protein Society·Jens LieboldElisabeth Schwarz

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.