Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation

Nature
Bernhard C LechtenbergStefan J Riedl

Abstract

Ubiquitination is a central process affecting all facets of cellular signalling and function. A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate. The RING-between-RING (RBR) family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases. The RBR family includes Parkin and HOIP, the central catalytic factor of the LUBAC (linear ubiquitin chain assembly complex). While structural insights into the RBR E3 ligases Parkin and HHARI in their overall auto-inhibited forms are available, no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely unknown. Here we present the first structure, to our knowledge, of the fully active human HOIP RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP RBR adopts a conformation markedly different from that of auto-inh...Continue Reading

References

Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Engin OzkanJohann Deisenhofer
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
Sep 29, 2006·The EMBO Journal·Takayoshi KirisakoKazuhiro Iwai
Jan 13, 2009·Nature Cell Biology·Fuminori TokunagaKazuhiro Iwai
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Mar 2, 2011·Acta Crystallographica. Section D, Biological Crystallography·Sergey StepanovRobert F Fischetti
Apr 2, 2011·Journal of Structural Biology·Mark P A Luna-VargasAnastassis Perrakis
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Gábor Bunkóczi, Randy J Read
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Aug 23, 2011·Nature Structural & Molecular Biology·Anna PlechanovováRonald T Hay
Dec 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yusuke SatoShuya Fukai
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Robert A NichollsGarib N Murshudov
Apr 25, 2012·Annual Review of Biochemistry·David Komander, Michael Rape
Jul 14, 2012·EMBO Reports·Benjamin StieglitzKatrin Rittinger
Jul 31, 2012·Nature·Anna PlechanovováRonald T Hay
Aug 21, 2012·Nature Structural & Molecular Biology·Hao DouDanny T Huang
May 11, 2013·Science·Jean-François TrempeKalle Gehring
Jun 4, 2013·The EMBO Journal·Tobias Wauer, David Komander
Jun 12, 2013·Biochimica Et Biophysica Acta·Meredith B MetzgerAllan M Weissman
Jun 19, 2013·Nature Communications·Donald E SprattGary S Shaw
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Aug 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christoph H EmmerichPhilip Cohen
Sep 24, 2013·PloS One·Donald E SprattGary S Shaw
Oct 22, 2013·Nature·Benjamin StieglitzKatrin Rittinger
Apr 5, 2014·Nature Structural & Molecular Biology·Christopher E Berndsen, Cynthia Wolberger
Apr 15, 2014·Molecular Cell·Paul R ElliottDavid Komander

❮ Previous
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Citations

Mar 2, 2016·Nature Chemical Biology·Kuan-Chuan PaoSatpal Virdee
Mar 24, 2016·Cell Research·Mikaela D StewartPeter S Brzovic
Mar 26, 2016·Cell Research·Kirby N Swatek, David Komander
Oct 3, 2013·PloS One·Dorthe LabontéMatthias Kneussel
Jun 30, 2011·PLoS Biology·Sébastien TauzinPatrick Legembre
Aug 4, 2016·Nature Reviews. Molecular Cell Biology·Lori Buetow, Danny T Huang
Jan 25, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexander F A Keszei, Frank Sicheri
Mar 3, 2017·Scientific Reports·Alain OregioniTom Frenkiel
May 20, 2017·Critical Reviews in Biochemistry and Molecular Biology·Petra EbnerFumiyo Ikeda
Jun 8, 2017·Structure·Karen M Dunkerley, Gary S Shaw
Jun 20, 2017·Journal of Molecular Biology·Adam J MiddletonCatherine L Day
Apr 5, 2017·Annual Review of Biochemistry·Ning Zheng, Nitzan Shabek
Feb 27, 2017·Journal of Molecular Biology·Pavel FilipčíkPeter D Mace
Jan 18, 2018·Infection and Immunity·Maarten F de Jong, Neal M Alto
Apr 21, 2018·Science·Connor Arkinson, Helen Walden
Apr 15, 2017·Biochemical Society Transactions·James M MurphyPatrick A Eyers
Jul 12, 2018·Nature·Christina GladkovaDavid Komander
Jan 24, 2018·Nature Reviews. Molecular Cell Biology·J Wade HarperJin-Mi Heo
Jun 18, 2016·EMBO Reports·Katja K DoveRachel E Klevit
Dec 16, 2019·Journal of Biomolecular NMR·Colin A SmithChristian Griesinger
Jul 18, 2020·Biochemical Society Transactions·Thomas R Cotton, Bernhard C Lechtenberg
Oct 13, 2016·The Biochemical Journal·Arno F AlpiHelen Walden
Jul 25, 2019·Frontiers in Physiology·Kirandeep K DeolEric R Strieter
Jan 31, 2020·Frontiers in Chemistry·Gunnar Dittmar, Konstanze F Winklhofer
Apr 5, 2020·Communications Biology·Daisuke OikawaFuminori Tokunaga
Jul 16, 2017·The Journal of Biological Chemistry·Sungjin ParkAlexander V Statsyuk
Jan 10, 2018·Scientific Reports·Luigi MartinoKatrin Rittinger
Jun 30, 2019·Cellular and Molecular Life Sciences : CMLS·Andrew N Bayne, Jean-François Trempe
Aug 5, 2020·Nature Chemical Biology·Peter D MabbittSatpal Virdee
Dec 4, 2016·Biochemical Society Transactions·Paul R Elliott
Jun 11, 2016·The Journal of Biological Chemistry·Erik WalindaMasahiro Shirakawa
Apr 18, 2017·Nature Structural & Molecular Biology·Atul KumarHelen Walden
Feb 29, 2020·Pharmacological Reviews·Bo ZhaoJun Yin
May 15, 2020·International Journal of Molecular Sciences·Daisuke OikawaFuminori Tokunaga
May 8, 2018·Nature Structural & Molecular Biology·Helen Walden, Katrin Rittinger
Apr 28, 2017·Open Biology·Katrin Rittinger, Fumiyo Ikeda
Jul 22, 2018·Cell Death and Differentiation·Anna L AaltoAnnika Meinander
Jul 4, 2018·Nature Structural & Molecular Biology·Véronique SauvéKalle Gehring

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Methods Mentioned

BETA
ubiquitination
PCR
size exclusion chromatography
ion exchange chromatography
X-ray
NMR
transfect

Software Mentioned

Phaser
Coot
Sculptor
PHENIX
PyMOL
XDS
XSCALE
ProSMART
GraphPad Prism
JBluIce

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