8jlk: Difference between revisions

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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=8jlk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jlk OCA], [https://pdbe.org/8jlk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jlk RCSB], [https://www.ebi.ac.uk/pdbsum/8jlk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jlk ProSAT]</span></td></tr>
 </table>
-== Function ==
-[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/TAAR1_MOUSE TAAR1_MOUSE] Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.<ref>PMID:15718104</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-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.
+Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis(1). They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling 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 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-HT(1A)R 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.
-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>
+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 Dec;624(7992):672-681. doi: 10.1038/s41586-023-06804-z. Epub 2023 , Nov 7. PMID:37935376<ref>PMID:37935376</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 <div class="pdbe-citations 8jlk" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
 <references/>