View source for 6dg7


==Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1==
<SX load='6dg7' size='340' side='right' viewer='molstar' caption='[[6dg7]], [[Resolution|resolution]] 3.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dg7]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DG7 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]] 3.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SRO:SEROTONIN'>SRO</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=6dg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dg7 OCA], [https://pdbe.org/6dg7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dg7 RCSB], [https://www.ebi.ac.uk/pdbsum/6dg7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dg7 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/5HT3A_MOUSE 5HT3A_MOUSE] This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
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== Publication Abstract from PubMed ==
The 5-HT3A serotonin receptor(1), a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies(2). Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT3A receptor in distinct conformations at 3.32 A and 3.89 A resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT3A receptor, serotonin-bound states underwent a large twisting motion in the ECD and TMD, leading to the opening of a 165 A permeation pathway. Notably, this motion results in the creation of lateral portals for ion permeation at the interface of the TMD and ICD. Combined with molecular dynamics simulations, these structures provide novel insights into conformational coupling across domains and functional modulation.

Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor.,Basak S, Gicheru Y, Rao S, Sansom MSP, Chakrapani S Nature. 2018 Nov;563(7730):270-274. doi: 10.1038/s41586-018-0660-7. Epub 2018 Oct, 31. PMID:30401837<ref>PMID:30401837</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
== References ==
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Basak S]]
[[Category: Chakrapani S]]