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Open data
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Basic information
Entry | Database: PDB / ID: 8jlr | ||||||
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Title | A77636-bound hTAAR1-Gs protein complex | ||||||
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Function / homology | ![]() Amine ligand-binding receptors / trace-amine receptor activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Xu, Z. / Guo, L.L. / Zhao, C. / Shen, S.Y. / Sun, J.P. / Shao, Z.H. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Ligand recognition and G-protein coupling of trace amine receptor TAAR1. 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 ...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 / ![]() 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 221.1 KB | Display | ![]() |
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PDB format | ![]() | 167 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 36405MC ![]() 8jljC ![]() 8jlkC ![]() 8jlnC ![]() 8jloC ![]() 8jlpC ![]() 8jlqC ![]() 8jsoC ![]() 8jspC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 2 types, 2 molecules AR
#1: Protein | Mass: 41879.465 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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#3: Protein | Mass: 54128.133 Da / Num. of mol.: 1 / Mutation: M29W,H124I,R128L Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() Gene: cybC, TAAR1 / Production host: ![]() ![]() ![]() |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules BY
#2: Protein | Mass: 39141.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
-Antibody / Non-polymers , 2 types, 2 molecules S![](data/chem/img/VRK.gif)
![](data/chem/img/VRK.gif)
#5: Antibody | Mass: 28666.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
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#6: Chemical | ChemComp-VRK / ( |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction![]() | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7933222 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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