We are not aware of any publication which cites or mentions this structure.
Time-resolved cryo-EM of G-protein activation by a GPCR.
Papasergi-Scott MM,
Pérez-Hernández 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)
Related entries:
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8geb,
8gec,
8ged,
8gee,
8gef,
8geg,
8geh,
8gei,
8gej,
8gfv,
8gfw,
8gfx,
8gfy,
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8gg0,
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PMID: 38480881
Abstract
G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit1. 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 Gs protein in complex with the β2-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 Gα switch regions and the α5 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 α-helical domain against the nucleotide-bound Ras-homology domain correlates with α5 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.
We are not aware of any publication which cites or mentions this structure.