7cky: Difference between revisions
m Protected "7cky" [edit=sysop:move=sysop] |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Cryo-EM structure of PW0464 bound dopamine receptor DRD1-Gs signaling complex== | |||
<StructureSection load='7cky' size='340' side='right'caption='[[7cky]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7cky]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CKY 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]] 3.2Å</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=G3U:6-[4-[3-[bis(fluoranyl)methoxy]pyridin-2-yl]oxy-2-methyl-phenyl]-1,5-dimethyl-pyrimidine-2,4-dione'>G3U</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=7cky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cky OCA], [https://pdbe.org/7cky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cky RCSB], [https://www.ebi.ac.uk/pdbsum/7cky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cky ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1. | |||
Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes.,Xiao P, Yan W, Gou L, Zhong YN, Kong L, Wu C, Wen X, Yuan Y, Cao S, Qu C, Yang X, Yang CC, Xia A, Hu Z, Zhang Q, He YH, Zhang DL, Zhang C, Hou GH, Liu H, Zhu L, Fu P, Yang S, Rosenbaum DM, Sun JP, Du Y, Zhang L, Yu X, Shao Z Cell. 2021 Feb 18;184(4):943-956.e18. doi: 10.1016/j.cell.2021.01.028. Epub 2021 , Feb 10. PMID:33571432<ref>PMID:33571432</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7cky" 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: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Shao Z]] | |||
[[Category: Yan W]] | |||
Latest revision as of 11:38, 17 October 2024
Cryo-EM structure of PW0464 bound dopamine receptor DRD1-Gs signaling complexCryo-EM structure of PW0464 bound dopamine receptor DRD1-Gs signaling complex
Structural highlights
Publication Abstract from PubMedDopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1. Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes.,Xiao P, Yan W, Gou L, Zhong YN, Kong L, Wu C, Wen X, Yuan Y, Cao S, Qu C, Yang X, Yang CC, Xia A, Hu Z, Zhang Q, He YH, Zhang DL, Zhang C, Hou GH, Liu H, Zhu L, Fu P, Yang S, Rosenbaum DM, Sun JP, Du Y, Zhang L, Yu X, Shao Z Cell. 2021 Feb 18;184(4):943-956.e18. doi: 10.1016/j.cell.2021.01.028. Epub 2021 , Feb 10. PMID:33571432[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||