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-Structure paper
タイトル | Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 28, Issue 3, Page 258-267, Year 2021 |
掲載日 | 2021年2月25日 |
著者 | Meng 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 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:33633398 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.1 - 4.5 Å |
構造データ | EMDB-23099: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, AHD and nanodisc mask out EMDB-23100: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, overall EMDB-23101: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, AHD and nanodisc mask out EMDB-23102: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, overall |
由来 |
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キーワード | SIGNALING PROTEIN / GPCR / NTSR1 / NTS / G protein / Nanodisc |