Author
Listed:
- Lulu Guo
(Shandong University
Shandong University School of Medicine)
- Jie Cheng
(Shandong University
Shandong University
School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education)
- Shuo Lian
(Qilu Hospital of Shandong University)
- Qun Liu
(Shandong University School of Medicine)
- Yan Lu
(Shandong University School of Medicine)
- Yuan Zheng
(School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education)
- Kongkai Zhu
(Shandong University)
- Minghui Zhang
(Qilu Hospital of Shandong University)
- Yalei Kong
(Shanghai Jiao Tong University School of Medicine
Shanghai Jiao Tong University
Shanghai Jiao Tong University School of Medicine)
- Chao Zhang
(Shandong University School of Medicine)
- Naikang Rong
(Shandong University School of Medicine)
- Yuming Zhuang
(Shandong University School of Medicine)
- Guoxing Fang
(Shandong University School of Medicine)
- Jingjing Jiang
(Shandong University School of Medicine)
- Tianyao Zhang
(Shandong University School of Medicine)
- Xiang Han
(Shandong University
Shandong University School of Medicine)
- Zili Liu
(Shandong University School of Medicine)
- Ming Xia
(Shandong Provincial Hospital Affiliated to Shandong First Medical University)
- Shangming Liu
(Shandong University)
- Lei Zhang
(Xi’an Jiaotong University)
- Stephen D. Liberles
(Harvard Medical School)
- Xiao Yu
(Shandong University)
- Yunfei Xu
(Qilu Hospital of Shandong University)
- Fan Yang
(Shandong University
Shandong University School of Medicine)
- Qian Li
(Shanghai Jiao Tong University School of Medicine
Shanghai Jiao Tong University
Shanghai Jiao Tong University School of Medicine
Shanghai Research Center for Brain Science and Brain-Inspired Intelligence)
- Jin-Peng Sun
(Shandong University
Shandong University School of Medicine
School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education)
Abstract
Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3–5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9–Gs or mTAAR9–Golf trimers in complex with β-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.
Suggested Citation
Lulu Guo & Jie Cheng & Shuo Lian & Qun Liu & Yan Lu & Yuan Zheng & Kongkai Zhu & Minghui Zhang & Yalei Kong & Chao Zhang & Naikang Rong & Yuming Zhuang & Guoxing Fang & Jingjing Jiang & Tianyao Zhang , 2023.
"Structural basis of amine odorant perception by a mammal olfactory receptor,"
Nature, Nature, vol. 618(7963), pages 193-200, June.
Handle:
RePEc:nat:nature:v:618:y:2023:i:7963:d:10.1038_s41586-023-06106-4
DOI: 10.1038/s41586-023-06106-4
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Cited by:
- Yu Qian & Zhengxiong Ma & Zhenmei Xu & Yaning Duan & Yangjie Xiong & Ruixue Xia & Xinyan Zhu & Zongwei Zhang & Xinyu Tian & Han Yin & Jian Liu & Jing Song & Yang Lu & Anqi Zhang & Changyou Guo & Lihua, 2024.
"Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation,"
Nature Communications, Nature, vol. 15(1), pages 1-12, December.
- Anastasiia Gusach & Yang Lee & Armin Nikpour Khoshgrudi & Elizaveta Mukhaleva & Ning Ma & Eline J. Koers & Qingchao Chen & Patricia C. Edwards & Fanglu Huang & Jonathan Kim & Filippo Mancia & Dmitry B, 2024.
"Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f,"
Nature Communications, Nature, vol. 15(1), pages 1-12, December.
- Jinzhe Cao & Shengyang Tao, 2024.
"Liquid-liquid reactions performed by cellular reactors,"
Nature Communications, Nature, vol. 15(1), pages 1-10, December.
- Gregory Zilberg & Alexandra K. Parpounas & Audrey L. Warren & Shifan Yang & Daniel Wacker, 2024.
"Molecular basis of human trace amine-associated receptor 1 activation,"
Nature Communications, Nature, vol. 15(1), pages 1-14, December.
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