View source for 8bl8


==Human serotonin 5-HT3A receptor (apo, active/distorted conformation)==
<StructureSection load='8bl8' size='340' side='right'caption='[[8bl8]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bl8]] 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=8BL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BL8 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]] 3.21&#8491;</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=8bl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bl8 OCA], [https://pdbe.org/8bl8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bl8 RCSB], [https://www.ebi.ac.uk/pdbsum/8bl8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bl8 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bl8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lopez-Sanchez U]]
[[Category: Nury H]]