8itf | pdb_00008itf

Cryo-EM structure of the DMCHA-bound mTAAR9-Gs complex

spinqualitylabelsall models 8itf, resolution 3.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8itf is a 6 chain structure with sequence from Homo sapiens, Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.46Å Ligands: 8IA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMed 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 receptors(1,2) (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 aversion(3-5). Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-G(s) or mTAAR9-G(olf) trimers in complex with beta-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D(3.32)W(6.48)Y(7.43) 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 G(s) and G(olf) by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and G(olf) coupling of an amine olfactory receptor. Structural basis of amine odorant perception by a mammal olfactory receptor.,Guo L, Cheng J, Lian S, Liu Q, Lu Y, Zheng Y, Zhu K, Zhang M, Kong Y, Zhang C, Rong N, Zhuang Y, Fang G, Jiang J, Zhang T, Han X, Liu Z, Xia M, Liu S, Zhang L, Liberles SD, Yu X, Xu Y, Yang F, Li Q, Sun JP Nature. 2023 Jun;618(7963):193-200. doi: 10.1038/s41586-023-06106-4. Epub 2023 , May 24. PMID:37225986 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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