This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
8blb
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8blb is ON HOLD Authors: Description: Category: Unreleased Structures) |
|||
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Human serotonin 5-HT3A receptor in complex with vortioxetine (nanodiscs, ECD, active/distorted conformation)== | |
| + | <StructureSection load='8blb' size='340' side='right'caption='[[8blb]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8blb]] 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=8BLB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BLB 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=VTX:Vortioxetine'>VTX</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=8blb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8blb OCA], [https://pdbe.org/8blb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8blb RCSB], [https://www.ebi.ac.uk/pdbsum/8blb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8blb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/5HT3A_HUMAN 5HT3A_HUMAN] Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.<ref>PMID:10521471</ref> <ref>PMID:12867984</ref> <ref>PMID:17392525</ref> <ref>PMID:9950429</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT(3) receptor (5-HT(3)R), which features two properties: VTX acts differently on rodent and human 5-HT(3)R, and VTX appears to suppress any subsequent response to agonists. Using a combination of cryo-EM, electrophysiology, voltage-clamp fluorometry and molecular dynamics, we show that VTX stabilizes a resting inhibited state of the mouse 5-HT(3)R and an agonist-bound-like state of human 5-HT(3)R, in line with the functional profile of the drug. We report four human 5-HT(3)R structures and show that the human receptor transmembrane domain is intrinsically fragile. We also explain the lack of recovery after VTX administration via a membrane partition mechanism. | ||
| - | + | Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT(3) receptors.,Lopez-Sanchez U, Munro LJ, Ladefoged LK, Pedersen AJ, Brun CC, Lyngby SM, Baud D, Juillan-Binard C, Pedersen MG, Lummis SCR, Bang-Andersen B, Schiott B, Chipot C, Schoehn G, Neyton J, Dehez F, Nury H, Kristensen AS Nat Struct Mol Biol. 2024 May 2. doi: 10.1038/s41594-024-01282-x. PMID:38698207<ref>PMID:38698207</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8blb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lopez-Sanchez U]] | ||
| + | [[Category: Nury H]] | ||
Current revision
Human serotonin 5-HT3A receptor in complex with vortioxetine (nanodiscs, ECD, active/distorted conformation)
| |||||||||||
