EMD-17756

Single-particle
2.92 Å
EMD-17756 Deposition: 28/06/2023
Map released: 09/08/2023
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-17756

Structure of the murine trace amine-associated receptor TAAR7f bound to N,N-dimethylcyclohexylamine (DMCH) in complex with mini-Gs trimeric G protein

EMD-17756

Single-particle
2.92 Å
EMD-17756 Deposition: 28/06/2023
Map released: 09/08/2023
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Lama glama, Mus musculus
Sample: A complex of mouse trace-amine associated receptor 7f solubilized in LMNG/CHS bound to N,N-dimethylcyclohexylamine and coupled to: Engineered guanine nucleotide-binding protein G(s) subunit alpha isoform short + Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 + Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 + Nanobody 35
Fitted models: 8pm2 (Avg. Q-score: 0.496)

Deposition Authors: Gusach A, Lee Y, Edwards PC, Huang F, Weyand SN, Tate CG
Molecular recognition of an aversive odorant by the murine trace amine-associated receptor TAAR7f.
PUBMED: 37461561
DOI: doi:10.1101/2023.07.07.547762
ISSN: 2692-8205
Abstract:
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 Gs 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.