ArticleProceedings of the National Academy of Sciences of the United States of America2020
The atomistic level structure for the activated human κ-opioid receptor bound to the full Gi protein and the MP1104 agonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 32 citations in OpenAlex.
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments.Communications chemistry · 2024Article
- Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure and Molecular Mechanism of Signaling for the Glucagon-like Peptide-1 Receptor Bound to Gs Protein and Exendin-P5 Biased Agonist.Journal of the American Chemical Society · 2023Article
- The dynamics of agonist-βNature chemistry · 2023Article
- Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes.iScience · 2023Article
- Molecular mechanism of biased signaling at the kappa opioid receptor.Nature communications · 2023Article
- Role of kappa-opioid and mu-opioid receptors in pruritus: Peripheral and central itch circuits.Experimental dermatology · 2022Article
- Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor.MedComm · 2022Review
- G protein coupling and activation of the metabotropic GABANature communications · 2022Article
- Opportunities and Challenges for In Silico Drug Discovery at Delta Opioid Receptors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Biased β-Agonists Favoring Gs over β-Arrestin for Individualized Treatment of Obstructive Lung Disease.Journal of personalized medicine · 2022Review
- Novel Molecular Targets of Antidepressants.Molecules (Basel, Switzerland) · 2022Review
- Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery.Handbook of experimental pharmacology · 2022Review
- Identification and characterization of an atypical Gαs-biased βProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structures and Agonist Binding Sites of Bitter Taste Receptor TAS2R5 Complexed with Gi Protein and Validated against Experiment.The journal of physical chemistry letters · 2021Article
- Specific Engineered G Protein Coupling to Histamine Receptors Revealed from Cellular Assay Experiments and Accelerated Molecular Dynamics Simulations.International journal of molecular sciences · 2021Article
- Ketamine Metabolite (2ACS chemical neuroscience · 2021Article
- Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.Future medicinal chemistry · 2021Article
Corrections and comments
- Commented on by
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state of human κOR complexed with both heterotrimeric Gi protein and MP1104 agonist. This structure resulted from long molecular dynamics (MD) and metadynamics (metaMD) simulations starting from the 3.1-Å X-ray structure of κOR-MP1104 after replacing the nanobody with the activated Gi protein and from the 3.5-Å cryo-EM structure of μOR-Gi complex after replacing the 168 missing residues. Using MD and metaMD we discovered interactions to the Gi protein with strong anchors to two intracellular loops and transmembrane helix 6 of the κOR. These anchors strengthen the binding, contributing to a contraction in the binding pocket but an expansion in the cytoplasmic region of κOR to accommodate G protein. These remarkable changes in κOR structure reveal that the anchors are essential for activation.
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.