@Article{Zhang2021,
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},
title={Cryo-EM structure of an activated GPCR--G protein complex in lipid nanodiscs},
journal={Nature Structural {\&} Molecular Biology},
year={2021},
month={Mar},
day={01},
volume={28},
number={3},
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--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{\thinspace}{\AA}. 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.},
issn={1545-9985},
doi={10.1038/s41594-020-00554-6},
url={https://doi.org/10.1038/s41594-020-00554-6}
}