8uo2: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 8uo2 is ON HOLD
+==CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class R)==
+<StructureSection load='8uo2' size='340' side='right'caption='[[8uo2]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8uo2]] is a 4 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=8UO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UO2 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]] 3.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G1I:(5R,6R)-6-(methylamino)-5,6,7,8-tetrahydronaphthalene-1,2,5-triol'>G1I</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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=8uo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uo2 OCA], [https://pdbe.org/8uo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uo2 RCSB], [https://www.ebi.ac.uk/pdbsum/8uo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uo2 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Galpha subunit(1). To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G-protein complex. By monitoring the transitions of the stimulatory G(s) protein in complex with the beta(2)-adrenergic receptor at short sequential time points after GTP addition, we identified the conformational trajectory underlying G-protein activation and functional dissociation from the receptor. Twenty structures generated from sequential overlapping particle subsets along this trajectory, compared to control structures, provide a high-resolution description of the order of main events driving G-protein activation in response to GTP binding. Structural changes propagate from the nucleotide-binding pocket and extend through the GTPase domain, enacting alterations to Galpha switch regions and the alpha5 helix that weaken the G-protein-receptor interface. Molecular dynamics simulations with late structures in the cryo-EM trajectory support that enhanced ordering of GTP on closure of the alpha-helical domain against the nucleotide-bound Ras-homology domain correlates with alpha5 helix destabilization and eventual dissociation of the G protein from the GPCR. These findings also highlight the potential of time-resolved cryo-EM as a tool for mechanistic dissection of GPCR signalling events.
-Authors:
+Time-resolved cryo-EM of G-protein activation by a GPCR.,Papasergi-Scott MM, Perez-Hernandez G, Batebi H, Gao Y, Eskici G, Seven AB, Panova O, Hilger D, Casiraghi M, He F, Maul L, Gmeiner P, Kobilka BK, Hildebrand PW, Skiniotis G Nature. 2024 May;629(8014):1182-1191. doi: 10.1038/s41586-024-07153-1. Epub 2024 , Mar 13. PMID:38480881<ref>PMID:38480881</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8uo2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Papasergi-Scott MM]]
+[[Category: Skiniotis G]]