8dpf: Difference between revisions
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==Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to lorcaserin== | ==Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to lorcaserin== | ||
<StructureSection load='8dpf' size='340' side='right'caption='[[8dpf]]' scene=''> | <StructureSection load='8dpf' size='340' side='right'caption='[[8dpf]], [[Resolution|resolution]] 2.84Å' 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=8DPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPF FirstGlance]. <br> | <table><tr><td colspan='2'>[[8dpf]] 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=8DPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPF 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=8dpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpf OCA], [https://pdbe.org/8dpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpf RCSB], [https://www.ebi.ac.uk/pdbsum/8dpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpf 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]] 2.84Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=T4U:(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine'>T4U</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=8dpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpf OCA], [https://pdbe.org/8dpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpf RCSB], [https://www.ebi.ac.uk/pdbsum/8dpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpf ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/5HT2C_HUMAN 5HT2C_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.<ref>PMID:12970106</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:7895773</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT(2C) serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT(2C) isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT(2C)-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities. | |||
Molecular insights into the regulation of constitutive activity by RNA editing of 5HT(2C) serotonin receptors.,Gumpper RH, Fay JF, Roth BL Cell Rep. 2022 Aug 16;40(7):111211. doi: 10.1016/j.celrep.2022.111211. PMID:35977511<ref>PMID:35977511</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8dpf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Fay JF]] | [[Category: Fay JF]] | ||
[[Category: Gumpper RH]] | [[Category: Gumpper RH]] | ||
[[Category: Roth BL]] | [[Category: Roth BL]] | ||