8e9y: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==CryoEM structure of miniGq-coupled hM3Dq in complex with CNO== | |||
<StructureSection load='8e9y' size='340' side='right'caption='[[8e9y]], [[Resolution|resolution]] 2.79Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e9y]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E9Y 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]] 2.79Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WE9:8-chloro-11-(4-methyl-4-oxo-4lambda~5~-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine'>WE9</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=8e9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e9y OCA], [https://pdbe.org/8e9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e9y RCSB], [https://www.ebi.ac.uk/pdbsum/8e9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e9y ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling(1-4). The muscarinic receptor-based DREADDs are the most widely used chemogenetic tools in neuroscience research. The G(q)-coupled DREADD (hM3Dq) is used to enhance neuronal activity, whereas the G(i/o)-coupled DREADD (hM4Di) is utilized to inhibit neuronal activity(5). Here we report four DREADD-related cryogenic electron microscopy high-resolution structures: a hM3Dq-miniG(q) complex and a hM4Di-miniG(o) complex bound to deschloroclozapine; a hM3Dq-miniG(q) complex bound to clozapine-N-oxide; and a hM3R-miniG(q) complex bound to iperoxo. Complemented with mutagenesis, functional and computational simulation data, our structures reveal key details of the recognition of DREADD chemogenetic actuators and the molecular basis for activation. These findings should accelerate the structure-guided discovery of next-generation chemogenetic tools. | |||
Molecular basis for selective activation of DREADD-based chemogenetics.,Zhang S, Gumpper RH, Huang XP, Liu Y, Krumm BE, Cao C, Fay JF, Roth BL Nature. 2022 Dec;612(7939):354-362. doi: 10.1038/s41586-022-05489-0. Epub 2022 , Nov 30. PMID:36450989<ref>PMID:36450989</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8e9y" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Fay JF]] | |||
[[Category: Roth BL]] | |||
[[Category: Zhang S]] | |||
Latest revision as of 12:34, 17 October 2024
CryoEM structure of miniGq-coupled hM3Dq in complex with CNOCryoEM structure of miniGq-coupled hM3Dq in complex with CNO
Structural highlights
Publication Abstract from PubMedDesigner receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling(1-4). The muscarinic receptor-based DREADDs are the most widely used chemogenetic tools in neuroscience research. The G(q)-coupled DREADD (hM3Dq) is used to enhance neuronal activity, whereas the G(i/o)-coupled DREADD (hM4Di) is utilized to inhibit neuronal activity(5). Here we report four DREADD-related cryogenic electron microscopy high-resolution structures: a hM3Dq-miniG(q) complex and a hM4Di-miniG(o) complex bound to deschloroclozapine; a hM3Dq-miniG(q) complex bound to clozapine-N-oxide; and a hM3R-miniG(q) complex bound to iperoxo. Complemented with mutagenesis, functional and computational simulation data, our structures reveal key details of the recognition of DREADD chemogenetic actuators and the molecular basis for activation. These findings should accelerate the structure-guided discovery of next-generation chemogenetic tools. Molecular basis for selective activation of DREADD-based chemogenetics.,Zhang S, Gumpper RH, Huang XP, Liu Y, Krumm BE, Cao C, Fay JF, Roth BL Nature. 2022 Dec;612(7939):354-362. doi: 10.1038/s41586-022-05489-0. Epub 2022 , Nov 30. PMID:36450989[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||