8jln: Difference between revisions
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==T1AM-bound hTAAR1-Gs protein complex== | |||
<StructureSection load='8jln' size='340' side='right'caption='[[8jln]], [[Resolution|resolution]] 3.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8jln]] 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=8JLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JLN FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.24Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UJF:4-[4-(2-azanylethyl)-2-iodanyl-phenoxy]phenol'>UJF</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jln OCA], [https://pdbe.org/8jln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jln RCSB], [https://www.ebi.ac.uk/pdbsum/8jln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jln ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 Dec;624(7992):672-681. doi: 10.1038/s41586-023-06804-z. Epub 2023 , Nov 7. PMID:37935376<ref>PMID:37935376</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8jln" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Guo LL]] | |||
[[Category: Shao ZH]] | |||
[[Category: Shen SY]] | |||
[[Category: Sun JP]] | |||
[[Category: Xu Z]] | |||
[[Category: Zhao C]] | |||
Latest revision as of 12:46, 17 October 2024
T1AM-bound hTAAR1-Gs protein complexT1AM-bound hTAAR1-Gs protein complex
Structural highlights
Publication Abstract from PubMedTrace-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 Dec;624(7992):672-681. doi: 10.1038/s41586-023-06804-z. Epub 2023 , Nov 7. PMID:37935376[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||