6OS9

human Neurotensin Receptor 1 (hNTSR1) - Gi1 Protein Complex in canonical conformation (C state)

Summary for 6OS9

• Entry DOI: 10.2210/pdb6os9/pdb
• EMDB information: 20180
• Descriptor: Neurotensin receptor type 1, JMV449, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total)
• Functional Keywords: gpcr, g-protein, complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 162891.89

Authors

Kato, H.E.,Zhang, Y.,Kobilka, B.K.,Skiniotis, G. (deposition date: 2019-05-01, release date: 2019-07-10, Last modification date: 2025-05-28)

Primary citation

Kato, H.E.,Zhang, Y.,Hu, H.,Suomivuori, C.M.,Kadji, F.M.N.,Aoki, J.,Krishna Kumar, K.,Fonseca, R.,Hilger, D.,Huang, W.,Latorraca, N.R.,Inoue, A.,Dror, R.O.,Kobilka, B.K.,Skiniotis, G.
Conformational transitions of a neurotensin receptor 1-Gi1complex.
Nature, 572:80-85, 2019

PubMed Abstract: Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and the response to pain. Here we present structures of human NTSR1 in complex with the agonist JMV449 and the heterotrimeric G protein, at a resolution of 3 Å. We identify two conformations: a canonical-state complex that is similar to recently reported GPCR-G complexes (in which the nucleotide-binding pocket adopts more flexible conformations that may facilitate nucleotide exchange), and a non-canonical state in which the G protein is rotated by about 45 degrees relative to the receptor and exhibits a more rigid nucleotide-binding pocket. In the non-canonical state, NTSR1 exhibits features of both active and inactive conformations, which suggests that the structure may represent an intermediate form along the activation pathway of G proteins. This structural information, complemented by molecular dynamics simulations and functional studies, provides insights into the complex process of G-protein activation.

PubMed: 31243364
DOI: 10.1038/s41586-019-1337-6

Experimental method

ELECTRON MICROSCOPY (3 Å)