Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design...

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Auteurs principaux:	Yuta Horie, Takafumi Suzuki, Jin Inoue, Tatsuro Iso, Geoffrey Wells, Terry W. Moore, Tsunehiro Mizushima, Albena T. Dinkova-Kostova, Takuma Kasai, Takashi Kamei, Seizo Koshiba, Masayuki Yamamoto
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2021
Sujets:	Biology (General) QH301-705.5
Accès en ligne:	https://doaj.org/article/b744783a8c5b4f278122faa72d2167f4
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spelling	oai:doaj.org-article:b744783a8c5b4f278122faa72d2167f42021-12-02T15:55:21ZMolecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism10.1038/s42003-021-02100-62399-3642https://doaj.org/article/b744783a8c5b4f278122faa72d2167f42021-05-01T00:00:00Zhttps://doi.org/10.1038/s42003-021-02100-6https://doaj.org/toc/2399-3642Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design of Nrf2 activators targeting the Keap1-Nrf2 interaction.Yuta HorieTakafumi SuzukiJin InoueTatsuro IsoGeoffrey WellsTerry W. MooreTsunehiro MizushimaAlbena T. Dinkova-KostovaTakuma KasaiTakashi KameiSeizo KoshibaMasayuki YamamotoNature PortfolioarticleBiology (General)QH301-705.5ENCommunications Biology, Vol 4, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yuta Horie Takafumi Suzuki Jin Inoue Tatsuro Iso Geoffrey Wells Terry W. Moore Tsunehiro Mizushima Albena T. Dinkova-Kostova Takuma Kasai Takashi Kamei Seizo Koshiba Masayuki Yamamoto Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
description	Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design of Nrf2 activators targeting the Keap1-Nrf2 interaction.
format	article
author	Yuta Horie Takafumi Suzuki Jin Inoue Tatsuro Iso Geoffrey Wells Terry W. Moore Tsunehiro Mizushima Albena T. Dinkova-Kostova Takuma Kasai Takashi Kamei Seizo Koshiba Masayuki Yamamoto
author_facet	Yuta Horie Takafumi Suzuki Jin Inoue Tatsuro Iso Geoffrey Wells Terry W. Moore Tsunehiro Mizushima Albena T. Dinkova-Kostova Takuma Kasai Takashi Kamei Seizo Koshiba Masayuki Yamamoto
author_sort	Yuta Horie
title	Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_short	Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_full	Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_fullStr	Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_full_unstemmed	Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_sort	molecular basis for the disruption of keap1–nrf2 interaction via hinge & latch mechanism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b744783a8c5b4f278122faa72d2167f4
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Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

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