7jvq: Difference between revisions
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==== | ==Cryo-EM structure of apomorphine-bound dopamine receptor 1 in complex with Gs protein== | ||
<StructureSection load='7jvq' size='340' side='right'caption='[[7jvq]]' scene=''> | <StructureSection load='7jvq' size='340' side='right'caption='[[7jvq]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7jvq]] 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=7JVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JVQ FirstGlance]. <br> | ||
</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=7jvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jvq OCA], [https://pdbe.org/7jvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jvq RCSB], [https://www.ebi.ac.uk/pdbsum/7jvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jvq ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3Å</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=OR9:(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol'>OR9</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=7jvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jvq OCA], [https://pdbe.org/7jvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jvq RCSB], [https://www.ebi.ac.uk/pdbsum/7jvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jvq ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/DRD1_HUMAN DRD1_HUMAN] Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The D1- and D2-dopamine receptors (D1R and D2R), which signal through G(s) and G(i), respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G(s) and D2R-G(i) signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system. | |||
Structural insights into the human D1 and D2 dopamine receptor signaling complexes.,Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang XP, Shen DD, Xu T, Liu YF, Wang Y, Guo J, Jiang Y, Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE Cell. 2021 Feb 18;184(4):931-942.e18. doi: 10.1016/j.cell.2021.01.027. Epub 2021 , Feb 10. PMID:33571431<ref>PMID:33571431</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7jvq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dopamine receptor 3D structures|Dopamine receptor 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: Cheng X]] | |||
[[Category: Guo J]] | |||
[[Category: Huang S]] | |||
[[Category: Huang X-P]] | |||
[[Category: Jiang H]] | |||
[[Category: Jiang Y]] | |||
[[Category: Krumm B]] | |||
[[Category: Liu H]] | |||
[[Category: Liu Y-F]] | |||
[[Category: Mao C]] | |||
[[Category: Melcher K]] | |||
[[Category: Roth BL]] | |||
[[Category: Sheng D-D]] | |||
[[Category: Wang L]] | |||
[[Category: Wang Y]] | |||
[[Category: Xu HE]] | |||
[[Category: Xu P]] | |||
[[Category: Xu T]] | |||
[[Category: Zhang C]] | |||
[[Category: Zhang Y]] | |||
[[Category: Zhou XE]] | |||
[[Category: Zhuang Y]] | |||
Latest revision as of 09:26, 21 November 2024
Cryo-EM structure of apomorphine-bound dopamine receptor 1 in complex with Gs proteinCryo-EM structure of apomorphine-bound dopamine receptor 1 in complex with Gs protein
Structural highlights
FunctionDRD1_HUMAN Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedThe D1- and D2-dopamine receptors (D1R and D2R), which signal through G(s) and G(i), respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G(s) and D2R-G(i) signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system. Structural insights into the human D1 and D2 dopamine receptor signaling complexes.,Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang XP, Shen DD, Xu T, Liu YF, Wang Y, Guo J, Jiang Y, Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE Cell. 2021 Feb 18;184(4):931-942.e18. doi: 10.1016/j.cell.2021.01.027. Epub 2021 , Feb 10. PMID:33571431[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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