View source for 8ggc


==CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #18 of 20)==
<StructureSection load='8ggc' size='340' side='right'caption='[[8ggc]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ggc]] 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=8GGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GGC 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]] 3.4&#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=8ggc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ggc OCA], [https://pdbe.org/8ggc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ggc RCSB], [https://www.ebi.ac.uk/pdbsum/8ggc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ggc ProSAT]</span></td></tr>
</table>
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ggc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Papasergi-Scott MM]]
[[Category: Skiniotis G]]