A hydrophobic low-complexity region regulates aggregation of the yeast pyruvate kinase Cdc19 into amyloid-like aggregates in vitro.

The Journal of Biological Chemistry
Erica GrignaschiPaolo Arosio

Abstract

Cells form stress granules (SGs) upon stress stimuli to protect sensitive proteins and RNA from degradation. In the yeast Saccharomyces cerevisiae, specific stresses such as nutrient starvation and heat-shock trigger recruitment of the yeast pyruvate kinase Cdc19 into SGs. This RNA-binding protein was shown to form amyloid-like aggregates that are physiologically reversible and essential for cell cycle restart after stress. Cellular Cdc19 exists in an equilibrium between a homotetramer and monomer state. Here, we show that Cdc19 aggregation in vitro is governed by protein quaternary structure, and we investigate the physical-chemical basis of Cdc19's assembly properties. Equilibrium shift toward the monomer state exposes a hydrophobic low-complexity region (LCR), which is prone to induce intermolecular interactions with surrounding proteins. We further demonstrate that hydrophobic/hydrophilic interfaces can trigger Cdc19 aggregation in vitro Moreover, we performed in vitro biophysical analyses to compare Cdc19 aggregates with fibrils produced by two known dysfunctional amyloidogenic peptides. We show that the Cdc19 aggregates share several structural features with pathological amyloids formed by human insulin and the Alzheimer'...Continue Reading

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·V SluzkyR Langer
Aug 11, 1982·Biochimica Et Biophysica Acta·J Slavík
Mar 31, 2000·Nature Structural Biology·T KlabundeJ C Sacchettini
Feb 2, 2002·Science·Matthew R ChapmanScott J Hultgren
Jul 18, 2002·Nature Reviews. Drug Discovery·James C Sacchettini, Jeffery W Kelly
Dec 20, 2003·Nature·Fred E Cohen, Jeffery W Kelly
Apr 7, 2007·Trends in Biochemical Sciences·Douglas M FowlerJeffery W Kelly
Jul 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Neal D HammerMatthew R Chapman
Aug 1, 2009·Cellular and Molecular Life Sciences : CMLS·Joel N Buxbaum, Natàlia Reixach
Jun 25, 2010·Molecular Microbiology·Morten S DueholmDaniel E Otzen
Dec 27, 2011·Trends in Microbiology·Luz P BlancoMatthew R Chapman
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ingrid MacindoeMargaret Sunde
Mar 13, 2012·Journal of Molecular Biology·Samuel I A CohenTuomas P J Knowles
Jun 12, 2012·Cell·Stephanie C Weber, Clifford P Brangwynne
Dec 10, 2013·Journal of the American Chemical Society·Paolo ArosioSara Linse
Jan 28, 2014·Journal of the American Chemical Society·Silvia CampioniRoland Riek
Feb 25, 2014·Trends in Pharmacological Sciences·Paolo ArosioTuomas P J Knowles
May 24, 2014·Nature Reviews. Molecular Cell Biology·Tuomas P J KnowlesChristopher M Dobson
Feb 3, 2015·Nature Chemical Biology·Céline GalvagnionChristopher M Dobson
Feb 17, 2015·Nature Structural & Molecular Biology·Samuel I A CohenSara Linse
Feb 27, 2015·Physical Chemistry Chemical Physics : PCCP·Paolo ArosioSara Linse
Oct 17, 2015·Molecular Cell·Huaiying ZhangAmy S Gladfelter
Nov 12, 2015·Frontiers in Cellular Neuroscience·Anaïs Aulas, Christine Vande Velde
Jan 8, 2016·Nature Protocols·Georg MeislTuomas P J Knowles
Jul 5, 2016·Cell·Salman F BananiMichael K Rosen
Nov 11, 2016·Nature·Roland Riek, David S Eisenberg
Feb 23, 2017·Nature Reviews. Molecular Cell Biology·Salman F BananiMichael K Rosen

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Citations

Jul 25, 2019·Angewandte Chemie·Miriam LinsenmeierPaolo Arosio
Jul 2, 2020·The Journal of Cell Biology·Kyle BegovichJames E Wilhelm
May 2, 2020·Current Genetics·Aleksandra V Sergeeva, Alexey P Galkin
Oct 8, 2020·Epigenetics & Chromatin·Saikat Bhattacharya, Jerry L Workman
Feb 3, 2021·Biophysical Chemistry·Fulvio Grigolato, Paolo Arosio
Apr 20, 2021·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Yiwen R ChenDaniel F Jarosz
Oct 8, 2021·Nature Cell Biology·Gea CereghettiMatthias Peter

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