7x2d
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of the tavapadon-bound D1 dopamine receptor and mini-Gs complex== | |
| + | <StructureSection load='7x2d' size='340' side='right'caption='[[7x2d]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7x2d]] is a 5 chain structure with sequence from [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=7X2D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X2D 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]] 3.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=86W:1,5-dimethyl-6-[2-methyl-4-[3-(trifluoromethyl)pyridin-2-yl]oxy-phenyl]pyrimidine-2,4-dione'>86W</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=7x2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x2d OCA], [https://pdbe.org/7x2d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x2d RCSB], [https://www.ebi.ac.uk/pdbsum/7x2d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x2d ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R. | ||
| - | + | Ligand recognition and biased agonism of the D1 dopamine receptor.,Teng X, Chen S, Nie Y, Xiao P, Yu X, Shao Z, Zheng S Nat Commun. 2022 Jun 8;13(1):3186. doi: 10.1038/s41467-022-30929-w. PMID:35676276<ref>PMID:35676276</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7x2d" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Dopamine receptor 3D structures|Dopamine receptor 3D structures]] | ||
| + | *[[Transducin 3D structures|Transducin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Teng X]] | ||
| + | [[Category: Zheng S]] | ||
Current revision
Cryo-EM structure of the tavapadon-bound D1 dopamine receptor and mini-Gs complex
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