Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains.

Proceedings of the National Academy of Sciences of the United States of America
Toshihiko OguraMasayuki Yamamoto

Abstract

Keap1 is a substrate adaptor of a Cullin 3-based E3 ubiquitin ligase complex that recognizes Nrf2, and also acts as a cellular sensor for xenobiotics and oxidative stresses. Nrf2 is a transcriptional factor regulating the expression of cytoprotective enzyme genes in response to such stresses. Under unstressed conditions Keap1 binds Nrf2 and results in rapid degradation of Nrf2 through the proteasome pathway. In contrast, upon exposure to oxidative and electrophilic stress, reactive cysteine residues in intervening region (IVR) and Broad complex, Tramtrack, and Bric-à-Brac domains of Keap1 are modified by electrophiles. This modification prevents Nrf2 from rapid degradation and induces Nrf2 activity by repression of Keap1. Here we report the structure of mouse Keap1 homodimer by single particle electron microscopy. Three-dimensional reconstruction at 24-A resolution revealed two large spheres attached by short linker arms to the sides of a small forked-stem structure, resembling a cherry-bob. Each sphere has a tunnel corresponding to the central hole of the beta-propeller domain, as determined by x-ray crystallography. The IVR domain appears to surround the core of the beta-propeller domain. The unexpected proximity of IVR to th...Continue Reading

References

Jan 1, 1996·Journal of Structural Biology·M van HeelM Schatz
Aug 15, 1998·Journal of Structural Biology·C SatoA Engel
Mar 10, 2001·Quarterly Reviews of Biophysics·M van HeelA Patwardhan
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Ramos-GomezT W Kensler
Jul 30, 2002·The Journal of Biological Chemistry·Laurie M Zipper, R Timothy Mulcahy
Aug 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Albena T Dinkova-KostovaPaul Talalay
Oct 1, 2003·Nature Genetics·Nobunao WakabayashiMasayuki Yamamoto
Feb 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nobunao WakabayashiPaul Talalay
Oct 12, 2004·The Journal of Biological Chemistry·Xuchu LiLesa J Beamer
Nov 17, 2004·Trends in Biochemical Sciences·Peter J Stogios, Gilbert G Privé
Dec 2, 2004·Molecular and Cellular Biology·Donna D ZhangMark Hannink
Dec 8, 2004·Archives of Biochemistry and Biophysics·Yasutake KatohMasayuki Yamamoto
Nov 19, 2005·Biochemical and Biophysical Research Communications·Hiromi OkawaMasayuki Yamamoto
Mar 2, 2006·Molecular Cell·Balasundaram PadmanabhanMasayuki Yamamoto
Aug 5, 2006·Advances in Enzyme Regulation·Makoto Kobayashi, Masayuki Yamamoto
Dec 26, 2006·Protein Science : a Publication of the Protein Society·Peter J StogiosGilbert G Privé
Mar 27, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jacqui M MarzecSteven R Kleeberger
Nov 15, 2007·Antioxidants & Redox Signaling·Dianne M WaltersSteven R Kleeberger
Jan 1, 2008·Mutation Research·William O Osburn, Thomas W Kensler
Feb 13, 2008·Molecular and Cellular Biology·Tae YamamotoMasayuki Yamamoto
Apr 18, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·William O OsburnThomas W Kensler
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nadia G InnamoratoAntonio Cuadrado

❮ Previous
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Citations

Mar 3, 2011·Archives of Toxicology·Liam Baird, Albena T Dinkova-Kostova
May 15, 2013·Trends in Pharmacological Sciences·Takafumi SuzukiMasayuki Yamamoto
Nov 8, 2011·The Proceedings of the Nutrition Society·Hyo Jung KimJong-Sang Kim
Jul 11, 2013·Journal of Medicinal Chemistry·Anthony J WilsonChristopher J Moody
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael McMahonJohn D Hayes
Aug 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Liam BairdAlbena T Dinkova-Kostova
Mar 2, 2011·The Journal of Biological Chemistry·Emilia KansanenAnna-Liisa Levonen
Jan 26, 2013·The Journal of Biological Chemistry·Peter CanningAlex N Bullock
May 8, 2010·Antioxidants & Redox Signaling·John D HayesAlbena T Dinkova-Kostova
Sep 8, 2011·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Tze Fang WongNobuo Yaegashi
May 19, 2011·Biochemistry. Biokhimii︠a︡·V O TkachevN K Zenkov
Sep 6, 2012·International Journal of Molecular Sciences·Yuusuke MaruyamaChikara Sato
Jan 9, 2013·Annual Review of Pharmacology and Toxicology·Qiang Ma
Jun 24, 2014·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Nisreen KweiderChristoph Jan Wruck
Mar 7, 2014·Journal of Cancer Research and Clinical Oncology·MingJun XiangXiaoLi Wang
Nov 2, 2014·Microscopy·Chikara SatoToshihiko Ogura
Oct 22, 2013·Genes & Development·Melba C Jaramillo, Donna D Zhang
Aug 12, 2015·International Journal of Molecular Sciences·Liliana Carmona-AparicioNoemí Cárdenas-Rodríguez
Jun 10, 2015·Free Radical Biology & Medicine·Peter CanningAlex N Bullock
Jun 29, 2015·Free Radical Biology & Medicine·Takafumi Suzuki, Masayuki Yamamoto
Jul 30, 2015·The International Journal of Biochemistry & Cell Biology·Dawadschargal DubielMichael Naumann
May 16, 2012·Free Radical Biology & Medicine·Brahm H SegalTimothy S Blackwell
Dec 27, 2011·Free Radical Biology & Medicine·Emilia KansanenAnna-Liisa Levonen
Mar 10, 2011·Nitric Oxide : Biology and Chemistry·Akira Uruno, Hozumi Motohashi
Jul 6, 2010·Nitric Oxide : Biology and Chemistry·Takaaki AkaikeHideshi Ihara
Sep 13, 2015·European Journal of Medicinal Chemistry·Atul D JainTerry W Moore
Jan 22, 2011·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keiko TaguchiMasayuki Yamamoto
Oct 1, 2010·Current Opinion in Structural Biology·Erik S ZimmermanNing Zheng
Jan 24, 2014·Biochemical Society Transactions·Peter Canning, Alex N Bullock
May 12, 2012·The International Journal of Biochemistry & Cell Biology·Sarah J ChappleGiovanni E Mann
Jun 27, 2012·Free Radical Biology & Medicine·Kai TakayaMasayuki Yamamoto

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