| Autor: |
Guo, Lulu, Cheng, Jie, Lian, Shuo, Liu, Qun, Lu, Yan, Zheng, Yuan, Zhu, Kongkai, Zhang, Minghui, Kong, Yalei, Zhang, Chao, Rong, Naikang, Zhuang, Yuming, Fang, Guoxing, Jiang, Jingjing, Zhang, Tianyao, Han, Xiang, Liu, Zili, Xia, Ming, Liu, Shangming, Zhang, Lei, Liberles, Stephen D., Yu, Xiao, Xu, Yunfei, Yang, Fan, Li, Qian, Sun, Jin-Peng |
| Zdroj: |
Nature; 20230101, Issue: Preprints p1-8, 8p |
| Abstrakt: |
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–Gsor mTAAR9–Golftrimers 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 D3.32W6.48Y7.43motif, 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 Gsand Golfby structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golfcoupling of an amine olfactory receptor. |
| Databáze: |
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