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==Structure of human class T GPCR TAS2R14-miniGs/gust complex with Aristolochic acid A.== | |||
<StructureSection load='8xql' size='340' side='right'caption='[[8xql]], [[Resolution|resolution]] 2.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8xql]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XQL 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]] 2.99Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=GOQ:8-methoxy-6-nitro-naphtho[1,2-e][1,3]benzodioxole-5-carboxylic+acid'>GOQ</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=8xql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xql OCA], [https://pdbe.org/8xql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xql RCSB], [https://www.ebi.ac.uk/pdbsum/8xql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xql ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents(1,2). TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications(3). Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and G(i1) proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery. | |||
Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.,Hu X, Ao W, Gao M, Wu L, Pei Y, Liu S, Wu Y, Zhao F, Sun Q, Liu J, Jiang L, Wang X, Li Y, Tan Q, Cheng J, Yang F, Yang C, Sun J, Hua T, Liu ZJ Nature. 2024 Jul;631(8020):459-466. doi: 10.1038/s41586-024-07569-9. Epub 2024 , May 22. PMID:38776963<ref>PMID:38776963</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8xql" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium perfringens]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Hu XL]] | |||
[[Category: Hua T]] | |||
[[Category: Liu ZJ]] | |||
[[Category: Wu LJ]] | |||
Latest revision as of 11:46, 14 July 2024
Structure of human class T GPCR TAS2R14-miniGs/gust complex with Aristolochic acid A.Structure of human class T GPCR TAS2R14-miniGs/gust complex with Aristolochic acid A.
Structural highlights
FunctionGBB1_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.[1] Publication Abstract from PubMedBitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents(1,2). TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications(3). Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and G(i1) proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery. Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.,Hu X, Ao W, Gao M, Wu L, Pei Y, Liu S, Wu Y, Zhao F, Sun Q, Liu J, Jiang L, Wang X, Li Y, Tan Q, Cheng J, Yang F, Yang C, Sun J, Hua T, Liu ZJ Nature. 2024 Jul;631(8020):459-466. doi: 10.1038/s41586-024-07569-9. Epub 2024 , May 22. PMID:38776963[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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