ArticlePloS one2013
A computationally designed water-soluble variant of a G-protein-coupled receptor: the human mu opioid receptor.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Activation dynamics of a water-soluble human mu-opioid receptor.The Journal of biological chemistry · 2026Article
- Solubilization of Membrane Proteins using designed protein WRAPS.bioRxiv : the preprint server for biology · 2025Article
- Article
- Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code.Nature communications · 2024Article
- Exploring GPCR conformational dynamics using single-molecule fluorescence.Methods (San Diego, Calif.) · 2024Review
- Protein Design: From the Aspect of Water Solubility and Stability.Chemical reviews · 2022Review
- Tyrosine 7.43 is important for mu-opioid receptor downstream signaling pathways activated by fentanyl.Frontiers in pharmacology · 2022Article
- Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines.Proteins · 2021Article
- Changing channels.Nature chemistry · 2021Article
- Membrane Protein Engineering with Rosetta.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity.Scientific reports · 2020Article
- Characterization of an engineered water-soluble variant of the full-length human mu opioid receptor.Journal of biomolecular structure & dynamics · 2020Article
- Molecular Interaction Between Butorphanol and κ-Opioid Receptor.Anesthesia and analgesia · 2020Article
- Water Soluble G-protein Coupled Receptor Enabled Biosensors.Translational perioperative and pain medicine · 2019Article
- QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Recent advances in automated protein design and its future challenges.Expert opinion on drug discovery · 2018Review
- All-Electronic Quantification of Neuropeptide-Receptor Interaction Using a Bias-Free Functionalized Graphene Microelectrode.ACS nano · 2018Article
- Quantifying the effect of ionic screening with protein-decorated graphene transistors.Biosensors & bioelectronics · 2017Article
- Article
- Membrane proteins: always an insoluble problem?Biochemical Society transactions · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
G-protein-coupled receptors (GPCRs) play essential roles in various physiological processes, and are widely targeted by pharmaceutical drugs. Despite their importance, studying GPCRs has been problematic due to difficulties in isolating large quantities of these membrane proteins in forms that retain their ligand binding capabilities. Creating water-soluble variants of GPCRs by mutating the exterior, transmembrane residues provides a potential method to overcome these difficulties. Here we present the first study involving the computational design, expression and characterization of water-soluble variant of a human GPCR, the human mu opioid receptor (MUR), which is involved in pain and addiction. An atomistic structure of the transmembrane domain was built using comparative (homology) modeling and known GPCR structures. This structure was highly similar to the subsequently determined structure of the murine receptor and was used to computationally design 53 mutations of exterior residues in the transmembrane region, yielding a variant intended to be soluble in aqueous media. The designed variant expressed in high yield in Escherichia coli and was water soluble. The variant shared structural and functionally related features with the native human MUR, including helical secondary structure and comparable affinity for the antagonist naltrexone (Kd = 65 nM). The roles of cholesterol and disulfide bonds on the stability of the receptor variant were also investigated. This study exemplifies the potential of the computational approach to produce water-soluble variants of GPCRs amenable for structural and functionally related characterization in aqueous solution.
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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.