ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structure of signaling-competent neurotensin receptor 1 obtained by directed evolution in Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 207 citations in OpenAlex.
- Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.Nature communications · 2026Article
- Stabilization versus flexibility: Detergent-dependent trade-offs in neurotensin receptor 1 GPCR ensembles.Protein science : a publication of the Protein Society · 2026Article
- RePol: A high-throughput screen for optimizing membrane protein solubilization and purification using polymers.Protein science : a publication of the Protein Society · 2026Article
- Stabilization versus flexibility: detergent-dependent trade-offs in neurotensin receptor 1 GPCR ensembles.bioRxiv : the preprint server for biology · 2025Article
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
- Re-evaluation of Cyclic Peptide Binding to Neurotensin Receptor 1 by Shifting the Peptide Register during Synthesis.ACS medicinal chemistry letters · 2025Article
- Dually Labeled Neurotensin NTSJournal of medicinal chemistry · 2024Article
- G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.International journal of molecular sciences · 2024Article
- Insights on the G protein-coupled receptor helix 8 solution structure and orientation using a neurotensin receptor 1 peptide.Protein science : a publication of the Protein Society · 2024Article
- Engineered Chimera Protein Constructs to Facilitate the Production of Heterologous Transmembrane Proteins inInternational journal of molecular sciences · 2024Review
- Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.Nature communications · 2023Article
- NMR sample optimization and backbone assignment of a stabilized neurotensin receptor.Journal of structural biology · 2023Article
- A Vaccinia-based system for directed evolution of GPCRs in mammalian cells.Nature communications · 2023Article
- A method for selectiveProtein science : a publication of the Protein Society · 2022Article
- GPCR structural characterization by NMR spectroscopy in solution.Acta biochimica et biophysica Sinica · 2022Review
- Immunomodulatory Role of Neuropeptides in the Cornea.Biomedicines · 2022Review
- Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.Communications biology · 2022Article
- Conformational selection guides β-arrestin recruitment at a biased G protein-coupled receptor.Science (New York, N.Y.) · 2022Article
- Effect of Ligands and Transducers on the Neurotensin Receptor 1 Conformational Ensemble.Journal of the American Chemical Society · 2022Article
- Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crystallography has advanced our understanding of G protein-coupled receptors, but low expression levels and instability in solution have limited structural insights to very few selected members of this large protein family. Using neurotensin receptor 1 (NTR1) as a proof of principle, we show that two directed evolution technologies that we recently developed have the potential to overcome these problems. We purified three neurotensin-bound NTR1 variants from Escherichia coli and determined their X-ray structures at up to 2.75 Å resolution using vapor diffusion crystallization experiments. A crystallized construct was pharmacologically characterized and exhibited ligand-dependent signaling, internalization, and wild-type-like agonist and antagonist affinities. Our structures are fully consistent with all biochemically defined ligand-contacting residues, and they represent an inactive NTR1 state at the cytosolic side. They exhibit significant differences to a previously determined NTR1 structure (Protein Data Bank ID code 4GRV) in the ligand-binding pocket and by the presence of the amphipathic helix 8. A comparison of helix 8 stability determinants between NTR1 and other crystallized G protein-coupled receptors suggests that the occupancy of the canonical position of the amphipathic helix is reduced to various extents in many receptors, and we have elucidated the sequence determinants for a stable helix 8. Our analysis also provides a structural rationale for the long-known effects of C-terminal palmitoylation reactions on G protein-coupled receptor signaling, receptor maturation, and desensitization.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.