7L0Q

Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, with AHD

Summary for 7L0Q

• Entry DOI: 10.2210/pdb7l0q/pdb
• Related: 7L0P
• EMDB information: 23099 23100
• Descriptor: Neurotensin receptor type 1, Neurotensin, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (5 entities in total)
• Functional Keywords: gpcr, ntsr1, nts, g protein, nanodisc, signaling protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 5
• Total formula weight: 128562.06

Authors

Zhang, M.,Gui, M.,Wang, Z.,Gorgulla, C.,Yu, J.J.,Wu, H.,Sun, Z.,Klenk, C.,Merklinger, L.,Morstein, L.,Hagn, F.,Pluckthun, A.,Brown, A.,Nasr, M.L.,Wagner, G. (deposition date: 2020-12-12, release date: 2021-01-06, Last modification date: 2024-10-09)

Primary citation

Zhang, M.,Gui, M.,Wang, Z.F.,Gorgulla, C.,Yu, J.J.,Wu, H.,Sun, Z.J.,Klenk, C.,Merklinger, L.,Morstein, L.,Hagn, F.,Pluckthun, A.,Brown, A.,Nasr, M.L.,Wagner, G.
Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs.
Nat.Struct.Mol.Biol., 28:258-267, 2021

PubMed 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 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.

PubMed: 33633398
DOI: 10.1038/s41594-020-00554-6

Experimental method

ELECTRON MICROSCOPY (4.3 Å)