Native structure protects SUMO proteins from aggregation into amyloid fibrils

Biomacromolecules
Raimon SabateSalvador Ventura

Abstract

SUMO proteins belong to the Ubiquitin-like protein family, all sharing a common fold and a similar mechanism of conjugation to target polypeptides. SUMO is ubiquitous in all eukaryotes and participates in many crucial pathways. Native SUMO proteins are highly soluble, a property that is exploited in biotechnology. Moreover, SUMO regulates the solubility of aggregation-prone proteins in neurodegenerative disorders. Despite these properties, we show here that human SUMO1, SUMO2, and SUMO3 proteins are at risk of aggregation into amyloid structures if their native conformation is perturbed. Aggregation is mediated by specific regions, which overlap with SUMO functional interfaces, illustrating a competition between function and aggregation. Aggregation of SUMOs might have important physiological implications because disruption of the SUMO pathway is lethal in different organisms. It appears that functional constraints make it difficult to avoid the competition between productive folding and deleterious aggregation in globular proteins, even for essential polypeptides.

References

Aug 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·W E KlunkD J Abraham
Apr 5, 1987·Journal of Molecular Biology·S Vijay-KumarW J Cook
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
Mar 27, 1999·Nature·S J Li, M Hochstrasser
Aug 2, 2001·Journal of Molecular Biology·J ZurdoC M Dobson
Aug 17, 2001·Journal of the American Chemical Society·J ZurdoC M Dobson
Dec 20, 2003·Nature·Christopher M Dobson
Mar 24, 2004·Seminars in Cell & Developmental Biology·Christopher M Dobson
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Salvador VenturaLuis Serrano
Jun 11, 2004·Annual Review of Biochemistry·Erica S Johnson
Sep 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jing SongYuan Chen
Apr 6, 2005·Molecular Cell·Ronald T Hay
Jun 3, 2005·Nature·David Reverter, Christopher D Lima
Jun 17, 2005·Nature·Daichi BabaMasahiro Shirakawa
Oct 4, 2005·Biochemical and Biophysical Research Communications·David OwerbachKurt M Bohren
Nov 24, 2005·The FEBS Journal·Thomas R Jahn, Sheena E Radford
Dec 20, 2005·Journal of Molecular Biology·Frederic RousseauJoost W H Schymkowitz
Mar 10, 2006·The Journal of Biological Chemistry·Christina-Maria HeckerIvan Dikic
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Magdalena I IvanovaDavid Eisenberg
Mar 28, 2006·Current Opinion in Structural Biology·Rebecca Nelson, David Eisenberg
Jun 8, 2006·Annual Review of Biochemistry·Fabrizio Chiti, Christopher M Dobson
Jul 11, 2006·Biochemical and Biophysical Research Communications·Erkang FeiGuanghui Wang
Dec 19, 2006·Biophysical Journal·Natalia Sánchez de GrootSalvador Ventura
Feb 28, 2007·BMC Bioinformatics·Oscar Conchillo-SoléSalvador Ventura
Apr 10, 2007·Trends in Biochemical Sciences·Gian Gaetano TartagliaMichele Vendruscolo
Jul 24, 2007·Computational Biology and Chemistry·Sukjoon YoonYoung Do Yoo
Aug 2, 2007·EMBO Reports·Elodie Monsellier, Fabrizio Chiti
Aug 28, 2007·Protein Engineering, Design & Selection : PEDS·Antonio TrovatoSilvio C E Tosatto
Nov 15, 2007·Nature Reviews. Molecular Cell Biology·Ruth Geiss-Friedlander, Frauke Melchior
May 27, 2008·Molecular Biology and Evolution·Yiwen Chen, Nikolay V Dokholyan
Jun 24, 2008·Chemical Society Reviews·Gian Gaetano Tartaglia, Michele Vendruscolo
Feb 17, 2009·Current Opinion in Structural Biology·Valerie Daggett, Alan R Fersht
Jun 6, 2009·The Journal of Biological Chemistry·Sarmistha MukherjeeJorge A Iñiguez-Lluhí
Jun 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sebastian PechmannMichele Vendruscolo
Jul 11, 2009·BMC Structural Biology·Kimon K FrousiosStavros J Hamodrakas
Aug 4, 2009·Trends in Biochemical Sciences·Natalia S de GrootSalvador Ventura
Aug 22, 2009·PLoS Computational Biology·Virginia Castillo, Salvador Ventura

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Citations

Sep 4, 2013·International Journal of Molecular Sciences·Patrizia MarinelliSalvador Ventura
May 6, 2014·International Journal of Biological Macromolecules·Vera A BorzovaBoris I Kurganov
Feb 26, 2014·Biomacromolecules·Ricardo Graña-MontesSalvador Ventura
May 8, 2018·International Journal of Molecular Sciences·Jordi PujolsSalvador Ventura
Oct 7, 2019·Proteins·Tathagata NandiSri Rama Koti Ainavarapu
Sep 25, 2017·Scientific Reports·Cristina BatlleSalvador Ventura
Oct 9, 2014·The Journal of Biological Chemistry·Javier Garcia-PardoSalvador Ventura
Jul 9, 2020·Computational and Structural Biotechnology Journal·Jaime SantosSalvador Ventura
May 24, 2021·Journal of Molecular Biology·Francisca PinheiroSalvador Ventura

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