View source for 7xtb


==Serotonin 6 (5-HT6) receptor-Gs-Nb35 complex==
<StructureSection load='7xtb' size='340' side='right'caption='[[7xtb]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xtb]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XTB 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7xtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xtb OCA], [https://pdbe.org/7xtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xtb RCSB], [https://www.ebi.ac.uk/pdbsum/7xtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xtb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/5HT6R_HUMAN 5HT6R_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35714614, PubMed:36989299, PubMed:37327704, PubMed:8522988). Also has a high affinity for tricyclic psychotropic drugs (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35714614). HTR6 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:35714614, PubMed:37327704). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of mTOR signaling (PubMed:23027611).[UniProtKB:P31388][UniProtKB:Q9R1C8]<ref>PMID:23027611</ref> <ref>PMID:35714614</ref> <ref>PMID:36989299</ref> <ref>PMID:37327704</ref> <ref>PMID:8522988</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of G(s), G(i,) or G(q) proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT(4), 5-HT(6), and 5-HT(7) with G(s), and 5-HT(4) with G(i1). The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for G(s) and G(i), respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with G(s) or G(i). Together, these results present a common mechanism of G(s) versus G(i) protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors.

GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.,Huang S, Xu P, Shen DD, Simon IA, Mao C, Tan Y, Zhang H, Harpsoe K, Li H, Zhang Y, You C, Yu X, Jiang Y, Zhang Y, Gloriam DE, Xu HE Mol Cell. 2022 Jul 21;82(14):2681-2695.e6. doi: 10.1016/j.molcel.2022.05.031. , Epub 2022 Jun 16. PMID:35714614<ref>PMID:35714614</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xtb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Gloriam DE]]
[[Category: Harpsoe K]]
[[Category: Huang S]]
[[Category: Jiang Y]]
[[Category: Li H]]
[[Category: Mao C]]
[[Category: Shen DD]]
[[Category: Simon IA]]
[[Category: Tan Y]]
[[Category: Xu HE]]
[[Category: Xu P]]
[[Category: You C]]
[[Category: Yu X]]
[[Category: Zhang H]]
[[Category: Zhang Y]]