N-terminal acetylation of α-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer.

Protein Science : a Publication of the Protein Society
Lijuan KangJean Baum

Abstract

The conformational properties of soluble α-synuclein, the primary protein found in patients with Parkinson's disease, are thought to play a key role in the structural transition to amyloid fibrils. In this work, we report that recombinant 100% N-terminal acetylated α-synuclein purified under mild physiological conditions presents as a primarily monomeric protein, and that the N-terminal acetyl group affects the transient secondary structure and fibril assembly rates of the protein. Residue-specific NMR chemical shift analysis indicates substantial increase in transient helical propensity in the first 9 N-terminal residues, as well as smaller long-range changes in residues 28-31, 43-46, and 50-66: regions in which the three familial mutations currently known to be causative of early onset disease are found. In addition, we show that the N-terminal acetylated protein forms fibrils that are morphologically similar to those formed from nonacetylated α-synuclein, but that their growth rates are slower. Our results highlight that N-terminal acetylation does not form significant numbers of dimers, tetramers, or higher molecular weight species, but does alter the conformational distributions of monomeric α-synuclein species in regions ...Continue Reading

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A ChakrabarttyR L Baldwin
Mar 26, 1998·Protein Science : a Publication of the Protein Society·R Aurora, G D Rose
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G SpillantiniM Goedert
Oct 3, 2000·The Journal of Biological Chemistry·B Polevoda, F Sherman
Oct 9, 2001·The Journal of Biological Chemistry·R Bussell, D Eliezer
Mar 23, 2002·Protein Science : a Publication of the Protein Society·Yunjun Wang, Oleg Jardetzky
Jan 1, 2003·Journal of Molecular Biology·Bogdan Polevoda, Fred Sherman
Mar 26, 2003·Journal of Biomolecular NMR·Haiyan ZhangDavid S Wishart
Feb 3, 2004·Annals of Neurology·Juan J ZarranzJusto G de Yebenes
Oct 7, 2004·Journal of the American Society for Mass Spectrometry·Summer L BernsteinJay R Winkler
Jan 6, 2005·The Journal of Biological Chemistry·Eric A GreenbaumBenoit I Giasson
Mar 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Rodolfo M RasiaClaudio O Fernández
Dec 13, 2005·Biochimica Et Biophysica Acta·Yoon-Hui SungDavid Eliezer
Nov 8, 2006·Protein Science : a Publication of the Protein Society·Joseph A MarshJulie D Forman-Kay
Aug 8, 2007·Journal of Molecular Biology·Yoon-Hui Sung, David Eliezer
Aug 13, 2008·Journal of the American Chemical Society·Andrés BinolfiClaudio O Fernández
Apr 7, 2009·Journal of Molecular Biology·Carla C RospigliosiDavid Eliezer
Jun 23, 2009·Current Protein & Peptide Science·Vladimir N Uversky, David Eliezer
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·David P SmithAlison E Ashcroft
Oct 5, 2010·Journal of the American Chemical Society·Stamatios LiokatisPhilipp Selenko
Dec 2, 2010·Proteins·Antonino NatalelloRita Grandori
Jan 5, 2011·PloS One·Matthew JohnsonDaniel P Mulvihill
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Wei WangQuyen Q Hoang
Mar 13, 2012·Protein Science : a Publication of the Protein Society·Adam J Trexler, Elizabeth Rhoades

❮ Previous
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Citations

Apr 26, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Sibylle E Eisbach, Tiago F Outeiro
Jan 22, 2014·Quarterly Reviews of Biophysics·Nicoletta PlotegherLuigi Bubacco
Aug 28, 2013·Neuromolecular Medicine·Katrin Eckermann
Jan 26, 2016·Nature·Francois-Xavier TheilletPhilipp Selenko
Feb 13, 2013·Journal of the American Chemical Society·Thomas GurryCollin M Stultz
Jun 6, 2014·Chemical Reviews·Francois-Xavier TheilletPhilipp Selenko
Oct 16, 2015·Biochimica Et Biophysica Acta·Laura PieriVirginie Redeker
Jan 23, 2015·Protein Science : a Publication of the Protein Society·Austin E SmithGary J Pielak
Aug 10, 2013·The FEBS Journal·Eduardo Coelho-CerqueiraCristian Follmer
Oct 16, 2012·Biochimica Et Biophysica Acta·L A WoodsA E Ashcroft
May 6, 2015·Journal of the American Chemical Society·Marco C MiottoClaudio O Fernández
Jan 1, 2013·Intrinsically Disordered Proteins·T Reid Alderson, John L Markley
Apr 18, 2014·Biophysical Journal·James M KriegerAlfonso De Simone
Mar 13, 2014·Journal of Molecular Biology·Sowmya B LokappaTobias S Ulmer
Oct 9, 2013·Journal of the American Chemical Society·Zhiping JiangJennifer C Lee
Aug 15, 2013·The Journal of Physical Chemistry. B·Carlo Camilloni, Michele Vendruscolo
Sep 20, 2016·Nature Communications·Giuliana FuscoAlfonso De Simone
Oct 21, 2016·International Journal of Biological Macromolecules·Dhiman GhoshSamir K Maji
Nov 11, 2015·Physical Chemistry Chemical Physics : PCCP·G RossettiP Carloni
Feb 24, 2015·RSC Advances·K SivanesamN Andersen
Jul 16, 2014·Nature Communications·William M HolmesTricia R Serio
Sep 4, 2015·Protein Science : a Publication of the Protein Society·Maria K Janowska, Jean Baum
Mar 19, 2013·FEBS Letters·Gina M MoriartyJean Baum
Dec 31, 2014·Experimental Neurobiology·David Snead, David Eliezer
Feb 1, 2019·The Journal of Biological Chemistry·David Snead, David Eliezer
Jul 25, 2019·Molecular Neurodegeneration·Richard M MeadeJody M Mason
Sep 26, 2015·Journal of Parkinson's Disease·Jacqueline Burré
Aug 18, 2016·The Journal of Biological Chemistry·Aditya IyerVinod Subramaniam
Jul 16, 2017·The Journal of Biological Chemistry·Gina M MoriartyJean Baum
Sep 6, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nazareno GonzálezClaudio O Fernández
Feb 6, 2020·Biomolecules·Marco Bisaglia, Luigi Bubacco

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