Structural highlights
Function
GBG1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
Publication Abstract from PubMed
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 Galpha(i1)beta(1)gamma(1) in two conformational states, resolved to resolutions of 4.1 and 4.2 A. 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.
Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs.,Zhang M, Gui M, Wang ZF, Gorgulla C, Yu JJ, Wu H, Sun ZJ, Klenk C, Merklinger L, Morstein L, Hagn F, Pluckthun A, Brown A, Nasr ML, Wagner G Nat Struct Mol Biol. 2021 Mar;28(3):258-267. doi: 10.1038/s41594-020-00554-6. , Epub 2021 Feb 25. PMID:33633398[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang M, Gui M, Wang ZF, Gorgulla C, Yu JJ, Wu H, Sun ZJ, Klenk C, Merklinger L, Morstein L, Hagn F, Plückthun A, Brown A, Nasr ML, Wagner G. Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs. Nat Struct Mol Biol. 2021 Mar;28(3):258-267. PMID:33633398 doi:10.1038/s41594-020-00554-6
