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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Main Authors:	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
Language:	English
Published:	Nature Publishing Group 2021-05-01
Series:	Communications Biology
Online Access:	https://doi.org/10.1038/s42003-021-02100-6

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spelling	doaj-b744783a8c5b4f278122faa72d2167f42021-05-16T11:21:18ZengNature Publishing GroupCommunications Biology2399-36422021-05-014111110.1038/s42003-021-02100-6Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanismYuta Horie0Takafumi Suzuki1Jin Inoue2Tatsuro Iso3Geoffrey Wells4Terry W. Moore5Tsunehiro Mizushima6Albena T. Dinkova-Kostova7Takuma Kasai8Takashi Kamei9Seizo Koshiba10Masayuki Yamamoto11Department of Medical Biochemistry, Tohoku University Graduate School of MedicineDepartment of Medical Biochemistry, Tohoku University Graduate School of MedicineTohoku Medical Megabank Organization, Tohoku UniversityDepartment of Medical Biochemistry, Tohoku University Graduate School of MedicineUCL School of Pharmacy, University College LondonDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Cancer Center, University of Illinois at ChicagoPicobiology Institute, Graduate School of Life Science, University of HyogoJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of DundeeLaboratory for Cellular Structural Biology, RIKEN Center for Biosystems Dynamics ResearchDepartment of Surgery, Tohoku University Graduate School of MedicineTohoku Medical Megabank Organization, Tohoku UniversityDepartment of Medical Biochemistry, Tohoku University Graduate School of MedicineUsing 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.https://doi.org/10.1038/s42003-021-02100-6
collection	DOAJ
language	English
format	Article
sources	DOAJ
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
spellingShingle	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 Communications Biology
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 Publishing Group
series	Communications Biology
issn	2399-3642
publishDate	2021-05-01
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.
url	https://doi.org/10.1038/s42003-021-02100-6
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Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

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