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Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor

Author

Listed:
  • Shuyan Dai

    (Central South University)

  • Lingzhi Qu

    (Central South University)

  • Jun Li

    (The First Affiliated Hospital of University of South China)

  • Ye Zhang

    (Central South University)

  • Longying Jiang

    (Central South University)

  • Hudie Wei

    (Central South University)

  • Ming Guo

    (Central South University)

  • Xiaojuan Chen

    (Central South University)

  • Yongheng Chen

    (Central South University)

Abstract

The aryl hydrocarbon receptor (AHR), a member of the basic helix–loop–helix (bHLH) Per–Arnt–Sim (PAS) family of transcription factors, plays important roles in regulating xenobiotic metabolism, cellular differentiation, stem cell maintenance, as well as immunity. More recently, AHR has gained significant interest as a drug target for the development of novel cancer immunotherapy drugs. Detailed understanding of AHR-ligand binding has been hampered for decades by the lack of a three-dimensional structure of the AHR PAS-B domain. Here, we present multiple crystal structures of the Drosophila AHR PAS-B domain, including its apo, ligand-bound, and AHR nuclear translocator (ARNT) PAS-B-bound forms. Together with biochemical and cellular assays, our data reveal structural features of the AHR PAS-B domain, provide insights into the mechanism of AHR ligand binding, and provide the structural basis for the future development of AHR-targeted therapeutics.

Suggested Citation

  • Shuyan Dai & Lingzhi Qu & Jun Li & Ye Zhang & Longying Jiang & Hudie Wei & Ming Guo & Xiaojuan Chen & Yongheng Chen, 2022. "Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33858-w
    DOI: 10.1038/s41467-022-33858-w
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    1. Wenfang Chen & Haley Hill & Alana Christie & Min Soo Kim & Eboni Holloman & Andrea Pavia-Jimenez & Farrah Homayoun & Yuanqing Ma & Nirav Patel & Paul Yell & Guiyang Hao & Qurratulain Yousuf & Allison , 2016. "Targeting renal cell carcinoma with a HIF-2 antagonist," Nature, Nature, vol. 539(7627), pages 112-117, November.
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    4. Sébastien Corre & Nina Tardif & Nicolas Mouchet & Héloïse M. Leclair & Lise Boussemart & Arthur Gautron & Laura Bachelot & Anthony Perrot & Anatoly Soshilov & Aljosja Rogiers & Florian Rambow & Erwan , 2018. "Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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