7um5: Difference between revisions
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==== | ==CryoEM structure of Go-coupled 5-HT5AR in complex with 5-CT== | ||
<StructureSection load='7um5' size='340' side='right'caption='[[7um5]]' scene=''> | <StructureSection load='7um5' size='340' side='right'caption='[[7um5]], [[Resolution|resolution]] 2.73Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7um5]] 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=7UM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UM5 FirstGlance]. <br> | ||
</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=7um5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7um5 OCA], [https://pdbe.org/7um5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7um5 RCSB], [https://www.ebi.ac.uk/pdbsum/7um5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7um5 ProSAT]</span></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]] 2.73Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8K3:3-(2-azanylethyl)-1~{H}-indole-5-carboxamide'>8K3</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=7um5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7um5 OCA], [https://pdbe.org/7um5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7um5 RCSB], [https://www.ebi.ac.uk/pdbsum/7um5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7um5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/5HT5A_HUMAN 5HT5A_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35610220, PubMed:35835867, PubMed:9865521). Also functions as a receptor for ergot alkaloid derivatives and other psychoactive substances (PubMed:35835867). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35610220, PubMed:35835867, PubMed:9865521). HTR5A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:35610220, PubMed:35835867, PubMed:9865521).<ref>PMID:35610220</ref> <ref>PMID:35835867</ref> <ref>PMID:9865521</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Serotonin receptors are important targets for established therapeutics and drug development as they are expressed throughout the human body and play key roles in cell signaling. There are 12 serotonergic G protein-coupled receptor members encoded in the human genome, of which the 5-hydroxytryptamine (5-HT)(5A) receptor (5-HT(5A)R) is the least understood and lacks selective tool compounds. Here, we report four high-resolution (2.73-2.80 A) structures of human 5-HT(5A)Rs, including an inactive state structure bound to an antagonist AS2674723 by crystallization and active state structures bound to a partial agonist lisuride and two full agonists, 5-carboxamidotryptamine (5-CT) and methylergometrine, by cryo-EM. Leveraging the new structures, we developed a highly selective and potent antagonist for 5-HT(5A)R. Collectively, these findings both enhance our understanding of this enigmatic receptor and provide a roadmap for structure-based drug discovery for 5-HT(5A)R. | |||
Inactive and active state structures template selective tools for the human 5-HT(5A) receptor.,Zhang S, Chen H, Zhang C, Yang Y, Popov P, Liu J, Krumm BE, Cao C, Kim K, Xiong Y, Katritch V, Shoichet BK, Jin J, Fay JF, Roth BL Nat Struct Mol Biol. 2022 Jul;29(7):677-687. doi: 10.1038/s41594-022-00796-6. , Epub 2022 Jul 14. PMID:35835867<ref>PMID:35835867</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7um5" 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__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Fay JF]] | |||
[[Category: Roth BL]] | |||
[[Category: Zhang S]] | |||