Wild-type human γD-crystallin promotes aggregation of its oxidation-mimicking, misfolding-prone W42Q mutant.

The Journal of Biological Chemistry
Eugene Serebryany, Jonathan A King

Abstract

Non-native protein conformers generated by mutation or chemical damage template aggregation of wild-type, undamaged polypeptides in diseases ranging from amyotrophic lateral sclerosis to cancer. We tested for such interactions in the natively monomeric human eye lens protein γd-crystallin, whose aggregation leads to cataract disease. The oxidation-mimicking W42Q mutant of γd-crystallin formed non-native polymers starting from a native-like state under physiological conditions. Aggregation occurred in the temperature range 35-45 °C, in which the mutant protein began to lose the native conformation of its N-terminal domain. Surprisingly, wild-type γd-crystallin promoted W42Q polymerization in a catalytic manner, even at mutant concentrations too low for homogeneous nucleation to occur. The presence of wild-type protein also downshifted the temperature range of W42Q aggregation. W42Q aggregation required formation of a non-native intramolecular disulfide bond but not intermolecular cross-linking. Transient WT/W42Q binding may catalyze this oxidative misfolding event in the mutant. That a more stable variant in a mixture can specifically promote aggregation of a less stable one rationalizes how extensive aggregation of rare damaged...Continue Reading

References

Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R J SiezenG B Benedek
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·M J BennettD Eisenberg
Oct 3, 1999·Methods in Enzymology·F Ferrone
May 10, 2001·Proceedings of the National Academy of Sciences of the United States of America·F RousseauL S Itzhaki
Feb 20, 2003·Protein Science : a Publication of the Protein Society·Melissa S Kosinski-Collins, Jonathan King
Aug 28, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Massimo Stefani, Christopher M Dobson
Jul 24, 2004·The Journal of Physiology·Richard McNultySteven Bassnett
Jul 27, 2004·Protein Science : a Publication of the Protein Society·Melissa S Kosinski-CollinsJonathan King
May 3, 2005·Experimental Eye Research·Roger J W Truscott
Jul 28, 2005·Protein Science : a Publication of the Protein Society·Shannon L FlaughJonathan King
May 16, 2006·Structure·Melanie J BennettDavid Eisenberg
Aug 8, 2006·The Journal of Biological Chemistry·Shannon L FlaughJonathan King
Aug 24, 2006·Journal of Molecular Biology·Kazuhiko AdachiFrank A Ferrone
Sep 20, 2006·Accounts of Chemical Research·Ronald Wetzel
Sep 11, 2007·Journal of Proteome Research·Peter G Hains, Roger J W Truscott
Oct 2, 2007·Protein Science : a Publication of the Protein Society·Ishara A MillsJonathan A King
May 23, 2008·Journal of Molecular Biology·Shimon BershteinDan S Tawfik
Sep 2, 2008·Biochimica Et Biophysica Acta·Peter G Hains, Roger J W Truscott
Dec 18, 2008·Nature Chemical Biology·Fabrizio Chiti, Christopher M Dobson
May 12, 2009·Biochemical and Biophysical Research Communications·Katarina LindahlOsten Ljunggren
Jun 6, 2009·Nature Structural & Molecular Biology·F Ulrich Hartl, Manajit Hayer-Hartl
Jun 9, 2009·Nature Cell Biology·Florence ClavagueraMarkus Tolnay
Sep 18, 2009·The Journal of Biological Chemistry·Kate L Moreau, Jonathan King
Oct 1, 2009·Physiological Reviews·Adriano Aguzzi, Anna Maria Calella
Jun 25, 2010·Neurobiology of Disease·Jean-Nicolas AudetJean-Pierre Julien
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ying WangGeorge B Benedek
Nov 27, 2010·Journal of Molecular Biology·Bryon MahlerZhengrong Wu
Jan 25, 2011·Nature Structural & Molecular Biology·Beena Krishnan, Lila M Gierasch
Feb 12, 2011·Trends in Ecology & Evolution·Patrik Nosil, Dolph Schluter
Mar 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Michael A Wride
Mar 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·R Michael, A J Bron
Mar 30, 2011·Nature Chemical Biology·Jie XuJoost Schymkowitz
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Payel DasRuhong Zhou
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Leslie I GradNeil R Cashman
Dec 7, 2011·Molecular Biology and Evolution·Michael Lynch
Apr 24, 2012·Trends in Molecular Medicine·Kate L Moreau, Jonathan A King
Aug 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Rainer WilckenAlan R Fersht

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Citations

Sep 23, 2018·The Journal of Biological Chemistry·Eugene SerebryanyEugene I Shakhnovich
Mar 19, 2016·Protein Science : a Publication of the Protein Society·Eugene SerebryanyJonathan A King
Mar 7, 2020·Journal of Biomolecular Structure & Dynamics·Shiwani RanaKalyan Sundar Ghosh
May 30, 2020·Journal of Biomolecular Structure & Dynamics·Shiwani Rana, Kalyan Sundar Ghosh
Sep 1, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·J A Domínguez-CalvaL Quintanar
Aug 6, 2020·International Journal of Molecular Sciences·Mareike RiedlMartin Haslbeck
Jul 16, 2016·The Journal of Biological Chemistry·Eugene SerebryanyEugene I Shakhnovich
Dec 1, 2015·Biophysics Reviews·Nicholas J Ray
Feb 12, 2021·Chembiochem : a European Journal of Chemical Biology·Megan A RochaRachel W Martin
Aug 2, 2021·Experimental Eye Research·Eugene SerebryanyLiliana Quintanar
Apr 10, 2020·Accounts of Chemical Research·Kyle W RoskampRachel W Martin
Jun 20, 2018·Journal of the American Chemical Society·Hongsuk KangRuhong Zhou
Jun 15, 2019·The Journal of Physical Chemistry. B·Rodrigo Aguayo-OrtizLaura Dominguez
Nov 21, 2019·Journal of Chemical Information and Modeling·Rodrigo Aguayo-Ortiz, Laura Dominguez

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