@article {Zhang2021, title = {Cryo-EM structure of an activated GPCR{\textendash}G protein complex in lipid nanodiscs}, journal = {Nature Structural \& Molecular Biology}, volume = {28}, number = {3}, year = {2021}, month = {Mar}, pages = {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{\textendash}G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and G$\alpha$i1$\beta$1$\gamma$1 in two conformational states, resolved to resolutions of 4.1 and 4.2{\th}inspace}\AA. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein{\textendash}protein interactions at the GPCR{\textendash}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.}, issn = {1545-9985}, doi = {10.1038/s41594-020-00554-6}, url = {https://doi.org/10.1038/s41594-020-00554-6}, author = {Zhang, Meng and Gui, Miao and Wang, Zi-Fu and Gorgulla, Christoph and Yu, James J. and Wu, Hao and Sun, Zhen-yu J. and Klenk, Christoph and Merklinger, Lisa and Morstein, Lena and Hagn, Franz and Pl{\"u}ckthun, Andreas and Brown, Alan and Nasr, Mahmoud L. and Wagner, Gerhard} }