8e9w
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8e9w]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E9W FirstGlance]. <br> | <table><tr><td colspan='2'>[[8e9w]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E9W FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WEC:11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine'>WEC</scene></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]] 2.69Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WEC:11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine'>WEC</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=8e9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e9w OCA], [https://pdbe.org/8e9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e9w RCSB], [https://www.ebi.ac.uk/pdbsum/8e9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e9w ProSAT]</span></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=8e9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e9w OCA], [https://pdbe.org/8e9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e9w RCSB], [https://www.ebi.ac.uk/pdbsum/8e9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e9w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ACM3_HUMAN ACM3_HUMAN] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. | [https://www.uniprot.org/uniprot/ACM3_HUMAN ACM3_HUMAN] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. | ||
| + | <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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8e9w" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
CryoEM structure of miniGq-coupled hM3Dq in complex with DCZ
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