Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator.
Journal, issue, pages	Cell Res, Vol. 35, Issue 4, Page 284-295, Year 2025
Publish date	Mar 21, 2025
Authors	Demeng Sun / Xiang Li / Qingning Yuan / Yuanxia Wang / Pan Shi / Huanhuan Zhang / Tao Wang / Wenjing Sun / Shenglong Ling / Yuanchun Liu / Jinglin Lai / Wenqin Xie / Wanchao Yin / Lei Liu / H Eric Xu / Changlin Tian /
PubMed Abstract	Biased allosteric modulators (BAMs) of G protein-coupled receptors (GPCRs) have been at the forefront of drug discovery owing to their potential to selectively stimulate therapeutically relevant ...Biased allosteric modulators (BAMs) of G protein-coupled receptors (GPCRs) have been at the forefront of drug discovery owing to their potential to selectively stimulate therapeutically relevant signaling and avoid on-target side effects. Although structures of GPCRs in complex with G protein or GRK in a BAM-bound state have recently been resolved, revealing that BAM can induce biased signaling by directly modulating interactions between GPCRs and these two transducers, no BAM-bound GPCR-arrestin complex structure has yet been determined, limiting our understanding of the full pharmacological profile of BAMs. Herein, we developed a chemical protein synthesis strategy to generate neurotensin receptor 1 (NTSR1) with defined hexa-phosphorylation at its C-terminus and resolved high-resolution cryo-EM structures (2.65-2.88 Å) of NTSR1 in complex with both β-arrestin1 and the BAM SBI-553. These structures revealed a unique "loop engagement" configuration of β-arrestin1 coupling to NTSR1 in the presence of SBI-553, markedly different from the typical "core engagement" configuration observed in the absence of BAMs. This configuration is characterized by the engagement of the intracellular loop 3 of NTSR1 with a cavity in the central crest of β-arrestin1, representing a previously unobserved, arrestin-selective conformation of GPCR. Our findings fill the critical knowledge gap regarding the regulation of GPCR-arrestin interactions and biased signaling by BAMs, which would advance the development of safer and more efficacious GPCR-targeted therapeutics.
External links	Cell Res / PubMed:40118988 / PubMed Central
Methods	EM (single particle)
Resolution	2.65 - 3.41 Å
Structure data	60578 8zyt EMDB-60578, PDB-8zyt: Cryo-EM structure of neurotensin receptor 1 in complex with beta-arrestin1 and SBI-553 (complex 3) Method: EM (single particle) / Resolution: 2.65 Å 60579 8zyu EMDB-60579, PDB-8zyu: Cryo-EM structure of neurotensin receptor 1 in complex with beta-arrestin1 and SBI-553 (complex 1) Method: EM (single particle) / Resolution: 2.65 Å 60583 8zyy EMDB-60583, PDB-8zyy: Cryo-EM structure of neurotensin receptor 1 in complex with beta-arrestin1 and SBI-553 (complex 2) Method: EM (single particle) / Resolution: 2.83 Å 63543 9m0d EMDB-63543, PDB-9m0d: Cryo-EM structure of neurotensin receptor 1 in complex with beta-arrestin 1 Method: EM (single particle) / Resolution: 3.41 Å
Chemicals	ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate ChemComp-SRW: 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl}(methyl)amino]ethan-1-ol
Source	homo sapiens (human) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN / neurotensin receptor / beta-arrestin1 / phosphorylation / intracellular agonist / SBI-553 / GPCR / Neurotensin receptore 1 / Complex / beta-arrestin 1