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| | '''Unreleased structure''' |
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| ==AMPH-bound hTAAR1-Gs protein complex==
| | The entry 8jso is ON HOLD |
| <StructureSection load='8jso' size='340' side='right'caption='[[8jso]], [[Resolution|resolution]] 3.40Å' scene=''>
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| == Structural highlights ==
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| <table><tr><td colspan='2'>[[8jso]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JSO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JSO FirstGlance]. <br>
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| </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</td></tr>
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| <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WE:(2S)-1-PHENYLPROPAN-2-AMINE'>1WE</scene></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jso OCA], [https://pdbe.org/8jso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jso RCSB], [https://www.ebi.ac.uk/pdbsum/8jso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jso ProSAT]</span></td></tr>
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| </table>
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| == Function ==
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| [https://www.uniprot.org/uniprot/GBB1_HUMAN 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.<ref>PMID:18611381</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Trace amine-associated receptors (TAARs), a group of biogenic amine receptors, play pivotal roles in neurological and metabolic homeostasis(1). They recognize diverse endogenous trace amines (ETAs) and subsequently activate a range of G protein subtype signaling pathways(2,3). Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders(4,5). However, the molecular mechanisms underlying its ability to recognize different ligands remain largely elusive. Here, we present nine cryo-electron microscopy (EM) structures, with eight showing human and mouse TAAR1 in 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 depicting 5-HT(1A)R in complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to ETAs 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 aid the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.
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| Ligand recognition and G protein coupling of trace amine receptor TAAR1.,Xu Z, Guo L, Yu J, Shen S, Wu C, Zhang W, Zhao C, Deng Y, Tian X, Feng Y, Hou H, Su L, Wang H, Guo S, Wang H, Wang K, Chen P, Zhao J, Zhang X, Yong X, Cheng L, Liu L, Yang S, Yang F, Wang X, Yu X, Xu Y, Sun JP, Yan W, Shao Z Nature. 2023 Nov 7. doi: 10.1038/s41586-023-06804-z. PMID:37935376<ref>PMID:37935376</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| | Description: |
| </div>
| | [[Category: Unreleased Structures]] |
| <div class="pdbe-citations 8jso" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__
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| </StructureSection>
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| [[Category: Escherichia coli]]
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| [[Category: Homo sapiens]]
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| [[Category: Large Structures]] | |
| [[Category: Mus musculus]]
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| [[Category: Guo LL]]
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| [[Category: Shao ZH]]
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| [[Category: Shen SY]]
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| [[Category: Sun JP]]
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| [[Category: Xu Z]]
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| [[Category: Zhao C]]
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