IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34892-4.html
   My bibliography  Save this article

Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB

Author

Listed:
  • Meghan H. Murray

    (Saint Louis University School of Medicine
    Washington University School of Medicine, University of Health Sciences & Pharmacy)

  • Aurore Cecile Valfort

    (University of Florida Genetics Institute)

  • Thomas Koelblen

    (University of Florida Genetics Institute)

  • Céline Ronin

    (NovAliX SAS)

  • Fabrice Ciesielski

    (NovAliX SAS)

  • Arindam Chatterjee

    (Saint Louis University School of Medicine)

  • Giri Babu Veerakanellore

    (Washington University School of Medicine, University of Health Sciences & Pharmacy
    University of Health Sciences & Pharmacy)

  • Bahaa Elgendy

    (Washington University School of Medicine, University of Health Sciences & Pharmacy
    University of Health Sciences & Pharmacy)

  • John K. Walker

    (Saint Louis University School of Medicine)

  • Lamees Hegazy

    (Washington University School of Medicine, University of Health Sciences & Pharmacy
    University of Health Sciences & Pharmacy)

  • Thomas P. Burris

    (University of Florida Genetics Institute)

Abstract

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB.

Suggested Citation

  • Meghan H. Murray & Aurore Cecile Valfort & Thomas Koelblen & Céline Ronin & Fabrice Ciesielski & Arindam Chatterjee & Giri Babu Veerakanellore & Bahaa Elgendy & John K. Walker & Lamees Hegazy & Thomas, 2022. "Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34892-4
    DOI: 10.1038/s41467-022-34892-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34892-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34892-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Gabriele Sulli & Amy Rommel & Xiaojie Wang & Matthew J. Kolar & Francesca Puca & Alan Saghatelian & Maksim V. Plikus & Inder M. Verma & Satchidananda Panda, 2018. "Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence," Nature, Nature, vol. 553(7688), pages 351-355, January.
    2. Laura A. Solt & Yongjun Wang & Subhashis Banerjee & Travis Hughes & Douglas J. Kojetin & Thomas Lundasen & Youseung Shin & Jin Liu & Michael D. Cameron & Romain Noel & Seung-Hee Yoo & Joseph S. Takaha, 2012. "Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists," Nature, Nature, vol. 485(7396), pages 62-68, May.
    3. Han Cho & Xuan Zhao & Megumi Hatori & Ruth T. Yu & Grant D. Barish & Michael T. Lam & Ling-Wa Chong & Luciano DiTacchio & Annette R. Atkins & Christopher K. Glass & Christopher Liddle & Johan Auwerx &, 2012. "Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β," Nature, Nature, vol. 485(7396), pages 123-127, May.
    4. Laura A. Solt & Naresh Kumar & Philippe Nuhant & Yongjun Wang & Janelle L. Lauer & Jin Liu & Monica A. Istrate & Theodore M. Kamenecka & William R. Roush & Dušica Vidović & Stephan C. Schürer & Jihong, 2011. "Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand," Nature, Nature, vol. 472(7344), pages 491-494, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Laura Isigkeit & Espen Schallmayer & Romy Busch & Lorene Brunello & Amelie Menge & Lewis Elson & Susanne Müller & Stefan Knapp & Alexandra Stolz & Julian A. Marschner & Daniel Merk, 2024. "Chemogenomics for NR1 nuclear hormone receptors," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Qixin Wang & Isaac Kirubakaran Sundar & Joseph H. Lucas & Jun-Gyu Park & Aitor Nogales & Luis Martinez-Sobrido & Irfan Rahman, 2023. "Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yasuko O. Abe & Hikari Yoshitane & Dae Wook Kim & Satoshi Kawakami & Michinori Koebis & Kazuki Nakao & Atsu Aiba & Jae Kyoung Kim & Yoshitaka Fukada, 2022. "Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Kameron Hahn & Isaac Kirubakaran Sundar, 2023. "Current Perspective on the Role of the Circadian Clock and Extracellular Matrix in Chronic Lung Diseases," IJERPH, MDPI, vol. 20(3), pages 1-13, January.
    4. Hengxu Liu & Shiqi Liu & Kun Wang & Tingran Zhang & Lian Yin & Jiaqi Liang & Yi Yang & Jiong Luo, 2022. "Time-Dependent Effects of Physical Activity on Cardiovascular Risk Factors in Adults: A Systematic Review," IJERPH, MDPI, vol. 19(21), pages 1-17, October.
    5. Seref Gul & Yasemin Kubra Akyel & Zeynep Melis Gul & Safak Isin & Onur Ozcan & Tuba Korkmaz & Saba Selvi & Ibrahim Danis & Ozgecan Savlug Ipek & Fatih Aygenli & Ali Cihan Taskin & Büşra Aytül Akarlar , 2022. "Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Li, Ying & Liu, Zengrong, 2015. "Dynamical mechanism of Bmal1/Rev-erbα loop in circadian clock," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 430(C), pages 126-135.
    7. Rongfeng Huang & Jianghui Chen & Meiyu Zhou & Haoran Xin & Sin Man Lam & Xiaoqing Jiang & Jie Li & Fang Deng & Guanghou Shui & Zhihui Zhang & Min-Dian Li, 2023. "Multi-omics profiling reveals rhythmic liver function shaped by meal timing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. David H. Sarrazin & Wilf Gardner & Carole Marchese & Martin Balzinger & Chockalingam Ramanathan & Marion Schott & Stanislav Rozov & Maxime Veleanu & Stefan Vestring & Claus Normann & Tomi Rantamäki & , 2024. "Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34892-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.