Cryo-EM structure of the cytosolic AhR complex

被引:30
作者
Wen, Zuoling [1 ,2 ]
Zhang, Yuebin [3 ]
Zhang, Beirong [2 ,4 ]
Hang, Yumo [5 ]
Xu, Li [6 ]
Chen, Yangsheng [6 ]
Xie, Qunhui [6 ]
Zhao, Qun [4 ]
Zhang, Lihua [4 ]
Li, Guohui [3 ]
Zhao, Bin [6 ]
Sun, Fei [1 ,2 ,7 ]
Zhai, Yujia [1 ]
Zhu, Yun [1 ]
机构
[1] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Key Lab Biomacromol, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Beijing, Peoples R China
[3] Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian, Peoples R China
[4] Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog R&A Ctr, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Liaoning, Peoples R China
[5] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathogen Biol, Wuhan 430030, Peoples R China
[6] Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China
[7] Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Core Facil Prot Sci, Beijing, Peoples R China
关键词
LIGAND-BINDING; PROTEIN INTERACTION; PAS DOMAINS; RECEPTOR; DIMERIZATION; IDENTIFICATION; RECOGNITION; MECHANISM; REVEALS; MICE;
D O I
10.1016/j.str.2022.12.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aryl hydrocarbon receptor (AhR) is an important ligand-activated transcription factor involved in the regula-tion 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 func-tions 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.
引用
收藏
页码:295 / +
页数:19
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