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-Structure paper
タイトル | Molecular recognition of an aversive odorant by the murine trace amine-associated receptor TAAR7f. |
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ジャーナル・号・ページ | bioRxiv, Year 2023 |
掲載日 | 2023年7月7日 |
![]() | 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 Verprintsev / Nagarajan Vaidehi / Simone N Weyand / Christopher G Tate / ![]() ![]() |
PubMed 要旨 | There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are ...There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein G and bound to the odorant N,N-dimethylcyclohexylamine (DMCH) to an overall resolution of 2.9 Å. DMCH is bound in a hydrophobic orthosteric binding site primarily through van der Waals interactions and a strong charge-charge interaction between the tertiary amine of the ligand and an aspartic acid residue. This site is distinct and non-overlapping with the binding site for the odorant propionate in the odorant receptor OR51E2. The structure, in combination with mutagenesis data and molecular dynamics simulations suggests that the activation of the receptor follows a similar pathway to that of the β-adrenoceptors, with the significant difference that DMCH interacts directly with one of the main activation microswitch residues. |
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手法 | EM (単粒子) |
解像度 | 2.92 Å |
構造データ | EMDB-17756, PDB-8pm2: |
化合物 | ![]() ChemComp-Y01: ![]() ChemComp-8IA: |
由来 |
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![]() | MEMBRANE PROTEIN / trace-amine associated receptor / TAAR / mTAAR7f / GPCR / receptor / G protein |