Cryo-EM structure of the cytosolic AhR complex

Zuoling Wen; Yuebin Zhang; Beirong Zhang; Yumo Hang; Li Xu; Yangsheng Chen; Qunhui Xie; Qun Zhao; Lihua Zhang; Guohui Li; Bin Zhao; Fei Sun; Yujia Zhai; Yun Zhu

doi:10.1016/j.str.2022.12.013

Cryo-EM structure of the cytosolic AhR complex

Structure. 2023 Mar 2;31(3):295-308.e4. doi: 10.1016/j.str.2022.12.013. Epub 2023 Jan 16.

Authors

Zuoling Wen¹, Yuebin Zhang², Beirong Zhang³, Yumo Hang⁴, Li Xu⁵, Yangsheng Chen⁵, Qunhui Xie⁵, Qun Zhao⁶, Lihua Zhang⁶, Guohui Li², Bin Zhao⁵, Fei Sun⁷, Yujia Zhai⁸, Yun Zhu⁹

Affiliations

¹ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China.
² State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
³ University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
⁴ Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁵ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
⁶ CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
⁷ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China; Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, CAS, Beijing, China. Electronic address: feisun@ibp.ac.cn.
⁸ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: yujia@ibp.ac.cn.
⁹ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhuyun@ibp.ac.cn.

PMID: 36649707
DOI: 10.1016/j.str.2022.12.013

Abstract

Aryl hydrocarbon receptor (AhR) is an important ligand-activated transcription factor involved in the regulation of various important physiological functions. Here, we report the cryo-EM structures of the Hsp90-AhR-p23 complex with or without bound XAP2, where the structure of the mouse AhR PAS-B domain is resolved. A highly conserved bridge motif of AhR is responsible for the interaction with the Hsp90 dimeric lumen. The ligand-free AhR PAS-B domain is attached to the Hsp90 dimer and is stabilized in the complex with bound XAP2. In addition, the DE-loop and a group of conserved pocket inner residues in the AhR PAS-B domain are found to be important for ligand binding. These results reveal the structural basis of the biological functions of AhR. Moreover, the protein purification method presented here allows the isolation of stable mouse AhR protein, which could be used to develop high-sensitivity biosensors for environmental pollutant detection.

Keywords: Hsp90; XAP2; aryl hydrocarbon receptor; cryo-electron microscopy; p23; single-particle analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cryoelectron Microscopy
Cytosol / metabolism
Gene Expression Regulation
HSP90 Heat-Shock Proteins* / metabolism
Mice
Receptors, Aryl Hydrocarbon* / chemistry

Substances

Receptors, Aryl Hydrocarbon
HSP90 Heat-Shock Proteins