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TitleCryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 3, Page 258-267, Year 2021
Publish dateFeb 25, 2021
AuthorsMeng Zhang / Miao Gui / Zi-Fu Wang / Christoph Gorgulla / James J Yu / Hao Wu / Zhen-Yu J Sun / Christoph Klenk / Lisa Merklinger / Lena Morstein / Franz Hagn / Andreas Plückthun / Alan Brown / Mahmoud L Nasr / Gerhard Wagner /
PubMed AbstractG-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 ...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 Gαβγ 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.
External linksNat Struct Mol Biol / PubMed:33633398 / PubMed Central
MethodsEM (single particle)
Resolution4.1 - 4.5 Å
Structure data

23099

7l0p

EMDB-23099: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, AHD and nanodisc mask out
PDB-7l0p: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, without AHD
Method: EM (single particle) / Resolution: 4.1 Å

23100

7l0q

EMDB-23100: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, overall
PDB-7l0q: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, with AHD
Method: EM (single particle) / Resolution: 4.3 Å

23101

7l0r

EMDB-23101: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, AHD and nanodisc mask out
PDB-7l0r: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, without AHD
Method: EM (single particle) / Resolution: 4.2 Å

23102

7l0s

EMDB-23102: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, overall
PDB-7l0s: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, with AHD
Method: EM (single particle) / Resolution: 4.5 Å

Source
  • rattus norvegicus (Norway rat)
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / GPCR / NTSR1 / NTS / G protein / Nanodisc

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