7ym8: Difference between revisions
New page: '''Unreleased structure''' The entry 7ym8 is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Cryo-EM structure of Nb29-alpha1AAR-miniGsq complex bound to oxymetazoline== | ||
<StructureSection load='7ym8' size='340' side='right'caption='[[7ym8]], [[Resolution|resolution]] 2.92Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7ym8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YM8 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]] 2.92Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J5C:6-~{tert}-butyl-3-(4,5-dihydro-1~{H}-imidazol-2-ylmethyl)-2,4-dimethyl-phenol'>J5C</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7ym8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ym8 OCA], [https://pdbe.org/7ym8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ym8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ym8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ym8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/ADA1A_HUMAN ADA1A_HUMAN] This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.<ref>PMID:18802028</ref> <ref>PMID:22120526</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alpha(1A-)adrenergic receptor (alpha(1A)AR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. alpha(1A)AR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human alpha(1A)AR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 A to 3.5 A. Our active and inactive alpha(1A)AR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of alpha(1A)AR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family. | |||
Structural basis of alpha(1A)-adrenergic receptor activation and recognition by an extracellular nanobody.,Toyoda Y, Zhu A, Kong F, Shan S, Zhao J, Wang N, Sun X, Zhang L, Yan C, Kobilka BK, Liu X Nat Commun. 2023 Jun 20;14(1):3655. doi: 10.1038/s41467-023-39310-x. PMID:37339967<ref>PMID:37339967</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7ym8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Kobilka BK]] | |||
[[Category: Liu X]] | |||
[[Category: Toyoda Y]] | |||
[[Category: Yan C]] | |||
[[Category: Zhu A]] | |||
Latest revision as of 14:47, 23 October 2024
Cryo-EM structure of Nb29-alpha1AAR-miniGsq complex bound to oxymetazolineCryo-EM structure of Nb29-alpha1AAR-miniGsq complex bound to oxymetazoline
Structural highlights
FunctionD9IEF7_BPT4 ADA1A_HUMAN This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.[1] [2] Publication Abstract from PubMedThe alpha(1A-)adrenergic receptor (alpha(1A)AR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. alpha(1A)AR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human alpha(1A)AR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 A to 3.5 A. Our active and inactive alpha(1A)AR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of alpha(1A)AR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family. Structural basis of alpha(1A)-adrenergic receptor activation and recognition by an extracellular nanobody.,Toyoda Y, Zhu A, Kong F, Shan S, Zhao J, Wang N, Sun X, Zhang L, Yan C, Kobilka BK, Liu X Nat Commun. 2023 Jun 20;14(1):3655. doi: 10.1038/s41467-023-39310-x. PMID:37339967[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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