Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to form Lys48-linked ubiquitin chains

The EMBO Journal
Weixiao LiuWei Li

Abstract

Cellular adaptation to proteotoxic stress at the endoplasmic reticulum (ER) depends on Lys48-linked polyubiquitination by ER-associated ubiquitin ligases (E3s) and subsequent elimination of ubiquitinated retrotranslocation products by the proteasome. The ER-associated E3 gp78 ubiquitinates misfolded proteins by transferring preformed Lys48-linked ubiquitin chains from the cognate E2 Ube2g2 to substrates. Here we demonstrate that Ube2g2 synthesizes linkage specific ubiquitin chains by forming an unprecedented homodimer: The dimerization of Ube2g2, mediated primarily by electrostatic interactions between two Ube2g2s, is also facilitated by the charged ubiquitin molecules. Mutagenesis studies show that Ube2g2 dimerization is required for ER-associated degradation (ERAD). In addition to E2 dimerization, we show that a highly conserved arginine residue in the donor Ube2g2 senses the presence of an aspartate in the acceptor ubiquitin to position only Lys48 of ubiquitin in proximity to the donor E2 active site. These results reveal an unanticipated mode of E2 self-association that allows the E2 to effectively engage two ubiquitins to specifically synthesize Lys48-linked ubiquitin chains.

References

Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·S FangA M Weissman
Jul 16, 2003·Molecular and Cellular Biology·Xaralabos VarelasMichael J Ellison
Jul 23, 2003·Nature Biotechnology·Junmin PengSteven P Gygi
Feb 8, 2005·Molecular Cell·Danny T HuangBrenda A Schulman
Sep 9, 2005·The EMBO Journal·Kaisa Haglund, Ivan Dikic
Jan 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bo ChenAllan M Weissman
Apr 4, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Ryoichi AraiShigeyuki Yokoyama
Sep 19, 2006·Nature Structural & Molecular Biology·Michael J EddinsCynthia Wolberger
Feb 21, 2007·Nature Cell Biology·Tommer Ravid, Mark Hochstrasser
Mar 7, 2008·The Journal of Biological Chemistry·Omar A Bazirgan, Randolph Y Hampton
Apr 29, 2008·Cellular and Molecular Life Sciences : CMLS·W Li, Y Ye
Feb 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Wei LiYihong Ye
Apr 9, 2009·Nature Reviews. Molecular Cell Biology·Brenda A Schulman, J Wade Harper
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Jun 6, 2009·Annual Review of Biochemistry·Raymond J Deshaies, Claudio A P Joazeiro
Oct 24, 2009·Nature Reviews. Molecular Cell Biology·Yihong Ye, Michael Rape
Nov 26, 2009·Biochemistry·Stephanie A Serniwka, Gary S Shaw
Jan 12, 2010·The Journal of Biological Chemistry·Yael DavidAmi Navon
Jan 23, 2010·The Journal of Biological Chemistry·Eric BourhisRami N Hannoush
May 1, 2010·Nature Protocols·Sjoerd J de VriesAlexandre M J J Bonvin
Aug 28, 2010·Molecular Cell·Monica C Rodrigo-BrenniDavid O Morgan
Dec 8, 2010·Cell Research·Siqi Liu, Zhijian J Chen
Dec 17, 2010·The Biochemical Journal·Dawn M WenzelRachel E Klevit
Oct 8, 2011·Trends in Cell Biology·Katherine E WickliffeMichael Rape
Oct 11, 2011·Critical Reviews in Biochemistry and Molecular Biology·Harish N Ramanathan, Yihong Ye
Nov 29, 2011·Nature Cell Biology·John C ChristiansonRon R Kopito
Apr 25, 2012·Annual Review of Biochemistry·David Komander, Michael Rape
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ender VolkanScott J Hultgren
Jul 31, 2012·Nature·Anna PlechanovováRonald T Hay

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Citations

Sep 19, 2014·Critical Reviews in Biochemistry and Molecular Biology·Dimitrios Zattas, Mark Hochstrasser
Mar 24, 2016·Cell Research·Mikaela D StewartPeter S Brzovic
Aug 20, 2015·Nucleic Acids Research·Pankaj KumarCynthia Wolberger
Nov 26, 2015·Scientific Reports·Adam J Middleton, Catherine L Day
Apr 14, 2016·Biochemical and Biophysical Research Communications·Fengyi GaoWei Li
Apr 25, 2015·Trends in Cell Biology·Michael J ClagueSylvie Urbé
Jun 20, 2017·Journal of Molecular Biology·Adam J MiddletonCatherine L Day
Jul 27, 2017·Journal of Cell Science·Michael L van de WeijerEmmanuel J H J Wiertz
Nov 18, 2018·Journal of Crohn's & Colitis·Antonio F Di NarzoKe Hao
Dec 13, 2016·Journal of Strength and Conditioning Research·Michael BehringerJoachim Mester
Oct 13, 2016·The Biochemical Journal·Arno F AlpiHelen Walden
Jul 25, 2019·Frontiers in Physiology·Kirandeep K DeolEric R Strieter
Dec 25, 2019·Nature Chemical Biology·Viduth K ChauguleHelen Walden
Oct 22, 2020·Science Signaling·Anna K L LiessSonja Lorenz
Dec 15, 2020·Biochimica Et Biophysica Acta. General Subjects·Satoshi NinagawaKazutoshi Mori

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