ArticleJournal of molecular biology2009
Thermostabilization of the neurotensin receptor NTS1.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- Protein Frustration Reveals Orthosteric and Allosteric Active Sites in GPCR:G Protein Complexes.Journal of chemical information and modeling · 2026Article
- Deceptive beauty of non-natural structures.Protein science : a publication of the Protein Society · 2026Review
- Stabilization versus flexibility: Detergent-dependent trade-offs in neurotensin receptor 1 GPCR ensembles.Protein science : a publication of the Protein Society · 2026Article
- Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs.Communications biology · 2026Review
- Stabilization versus flexibility: detergent-dependent trade-offs in neurotensin receptor 1 GPCR ensembles.bioRxiv : the preprint server for biology · 2025Article
- The Nature of Nanodisc Lipids Influences Fragment-Based Drug Discovery Results.Chemical biology & drug design · 2025Article
- Engineering G protein-coupled receptors for stabilization.Protein science : a publication of the Protein Society · 2024Article
- Recovery of the histamine HScientific reports · 2023Article
- Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein-Coupled Receptors in Live Cells.Journal of the American Chemical Society · 2023Article
- Fluorescence-Detection Size-Exclusion Chromatography-Based Thermostability Assay for Membrane Proteins.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
- Yeast-based directed-evolution for high-throughput structural stabilization of G protein-coupled receptors (GPCRs).Scientific reports · 2022Article
- Membrane Protein Production in Escherichia coli: Protocols and Rules.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Novel Application of Geometric Morphometrics with Principal Component Analysis to Existing G Protein-Coupled Receptor (GPCR) Structures.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Engineering of Challenging G Protein-Coupled Receptors for Structure Determination and Biophysical Studies.Molecules (Basel, Switzerland) · 2021Review
- Efficient production of a functional G protein-coupled receptor in E. coli for structural studies.Journal of biomolecular NMR · 2021Article
- An improved fluorescent tag and its nanobodies for membrane protein expression, stability assay, and purification.Communications biology · 2020Article
- Theoretical identification of thermostabilizing amino acid mutations for G-protein-coupled receptors.Biophysical reviews · 2020Review
- Machine Learning for Prioritization of Thermostabilizing Mutations for G-Protein Coupled Receptors.Biophysical journal · 2019Article
- Prediction of Conformation Specific Thermostabilizing Mutations for Class A G Protein-Coupled Receptors.Journal of chemical information and modeling · 2019Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Structural studies on G-protein-coupled receptors have been hampered for many years by their instability in detergent solution and by the number of potential conformations that receptors can adopt. Recently, the structures of the beta(1) and beta(2) adrenergic receptors and the adenosine A(2a) receptor were determined in the antagonist-bound state, a receptor conformation that is thought to be more stable than the agonist-bound state. In contrast to these receptors, the neurotensin (NT) receptor NTS1 is much less stable in detergent solution. We have therefore used a systematic mutational approach coupled with activity assays to identify receptor mutants suitable for crystallization, both alone and in complex with the peptide agonist NT. The best receptor mutant NTS1-7m contained four point mutations. It showed increased stability compared to the wild-type receptor, in the absence of ligand, after solubilization with a variety of detergents. In addition, NTS1-7m bound to NT was more stable than unliganded NTS1-7m. Of the four thermostabilizing mutations, only one residue (A86L) is predicted to be in the lipid environment. In contrast, I260A appears to be buried within the transmembrane helix bundle, F342A may form a distant part of the putative ligand-binding site, whereas F358A is likely to be in a region that is important for receptor activation. NTS1-7m binds NT with a similar affinity for the wild-type receptor. However, agonist dissociation was slower, and NTS1-7m activated G-proteins poorly. The affinity of NTS1-7m for the antagonist SR48692 was also lower than that of the wild-type receptor. Thus, we have successfully stabilized NTS1 in an agonist-binding conformation that does not efficiently couple to G-proteins.
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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.