EMD-23099
Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, AHD and nanodisc mask out
EMD-23099
Single-particle4.1 Å
Deposition: 12/12/2020
Map released: 06/01/2021
Last modified: 06/11/2024
Sample Organism:
Homo sapiens,
Rattus norvegicus
Sample: NTS-NTSR1-Gi complex in lipid nanodisc
Fitted models: 7l0p (Avg. Q-score: 0.404)
Deposition Authors: Zhang M , Gui M
Sample: NTS-NTSR1-Gi complex in lipid nanodisc
Fitted models: 7l0p (Avg. Q-score: 0.404)
Deposition Authors: Zhang M , Gui M
Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs.
Zhang M ,
Gui M ,
Wang ZF,
Gorgulla C,
Yu JJ,
Wu H ,
Sun ZJ,
Klenk C ,
Merklinger L,
Morstein L,
Hagn F ,
Pluckthun A ,
Brown A ,
Nasr ML,
Wagner G
(2021) Nat Struct Mol Biol , 28 , 258 - 267
(2021) Nat Struct Mol Biol , 28 , 258 - 267
Abstract:
G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR-G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and Gαi1β1γ1 in two conformational states, resolved to resolutions of 4.1 and 4.2 Å. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein-protein interactions at the GPCR-G protein interface as compared to structures obtained in detergent micelles. The findings show that the lipid membrane modulates the structure and dynamics of complex formation and provide a molecular explanation for the stronger interaction between GPCRs and G proteins in lipid bilayers. We propose an allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling.
G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR-G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and Gαi1β1γ1 in two conformational states, resolved to resolutions of 4.1 and 4.2 Å. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein-protein interactions at the GPCR-G protein interface as compared to structures obtained in detergent micelles. The findings show that the lipid membrane modulates the structure and dynamics of complex formation and provide a molecular explanation for the stronger interaction between GPCRs and G proteins in lipid bilayers. We propose an allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling.