Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Ligand recognition and G-protein coupling of trace amine receptor TAAR1.
Journal, issue, pages	Nature, Vol. 624, Issue 7992, Page 672-681, Year 2023
Publish date	Nov 7, 2023
Authors	Zheng Xu / Lulu Guo / Jingjing Yu / Siyuan Shen / Chao Wu / Weifeng Zhang / Chang Zhao / Yue Deng / Xiaowen Tian / Yuying Feng / Hanlin Hou / Lantian Su / Hongshuang Wang / Shuo Guo / Heli Wang / Kexin Wang / Peipei Chen / Jie Zhao / Xiaoyu Zhang / Xihao Yong / Lin Cheng / Lunxu Liu / Shengyong Yang / Fan Yang / Xiaohui Wang / Xiao Yu / Yunfei Xu / Jin-Peng Sun / Wei Yan / Zhenhua Shao /
PubMed Abstract	Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis. They recognize diverse endogenous trace amines and ...Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HTR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.
External links	Nature / PubMed:37935376
Methods	EM (single particle)
Resolution	2.84 - 3.65 Å
Structure data	36399 8jlj EMDB-36399, PDB-8jlj: T1AM-bound mTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.1 Å 36400 8jlk EMDB-36400, PDB-8jlk: Ulotaront(SEP-363856)-bound mTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.22 Å 36401 8jln EMDB-36401, PDB-8jln: T1AM-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.24 Å 36402 8jlo EMDB-36402, PDB-8jlo: Ulotaront(SEP-363856)-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.52 Å 36403 8jlp EMDB-36403, PDB-8jlp: Ralmitaront(RO-6889450)-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.23 Å 36404 8jlq EMDB-36404, PDB-8jlq: Fenoldopam-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 2.84 Å 36405 8jlr EMDB-36405, PDB-8jlr: A77636-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.0 Å 36625 8jso EMDB-36625, PDB-8jso: AMPH-bound hTAAR1-Gs protein complex Method: EM (single particle) / Resolution: 3.4 Å 36626 8jsp EMDB-36626, PDB-8jsp: Ulotaront(SEP-363856)-bound Serotonin 1A (5-HT1A) receptor-Gi complex Method: EM (single particle) / Resolution: 3.65 Å
Chemicals	ChemComp-UJF: 4-[4-(2-azanylethyl)-2-iodanyl-phenoxy]phenol ChemComp-UJL: 1-[(7~{S})-5,7-dihydro-4~{H}-thieno[2,3-c]pyran-7-yl]-~{N}-methyl-methanamine ChemComp-UJU: 5-ethyl-4-methyl-~{N}-[4-[(2~{S})-morpholin-2-yl]phenyl]-1~{H}-pyrazole-3-carboxamide ChemComp-G3C: (1R)-6-chloranyl-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol ChemComp-VRK: (1~{S},3~{R})-3-(1-adamantyl)-1-(aminomethyl)-3,4-dihydro-1~{H}-isochromene-5,6-diol ChemComp-1WE: (2S)-1-phenylpropan-2-amine / Dextroamphetamine
Source	homo sapiens (human) mus musculus (house mouse) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN/IMMUNE SYSTEM / Complex / Agonist / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex