ArticleNature2017
Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 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
115 citing papers in PubMed, 242 citations in OpenAlex.
- Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications.Pharmacology research & perspectives · 2026Review
- Uncovering Allosteric Signaling Pathways of GLP-1R via Molecular Dynamics and Network Theory.Research square · 2026Article
- Differential Modulation of GLP-1R by Dietary Ginsenosides Points to a Putative Extracellular Allosteric Site.International journal of molecular sciences · 2026Article
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Discovery and optimization of novel indolecarboxylic acid derivative as potent glucagon-like peptide‑1 receptor agonists.Molecular diversity · 2026Article
- GLP-1 receptor and Mitochondria-ER Contact Sites: an emerging mechanism of metabolic regulation.Frontiers in physiology · 2026Review
- Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders.Frontiers in pharmacology · 2026Review
- Molecular Mechanisms and Antidiabetic Effects of Mango (International journal of molecular sciences · 2025Article
- Roles of glucagon-like peptide 1 receptor agonists in immune cell biology and autoimmune/autoinflammatory diseases.Cell & bioscience · 2025Review
- Editorial to the Special Issue "Theoretical and Computational Polymer Science: Physics, Chemistry, and Biology".Polymers · 2025Article
- Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS.Nature structural & molecular biology · 2025Article
- Allosteric targeted drug delivery for enhanced blood-brain barrier penetration via mimicking transmembrane domain interactions.Nature communications · 2025Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Focus on Glucagon-like Peptide-1 Target: Drugs Approved or Designed to Treat Obesity.International journal of molecular sciences · 2025Review
- A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist.Drug design, development and therapy · 2025Review
- GLP-1 receptor agonists: exploration of transformation from metabolic regulation to multi-organ therapy.Frontiers in pharmacology · 2025Review
- Polymers in Physics, Chemistry and Biology: Behavior of Linear Polymers in Fractal Structures.Polymers · 2024Review
- A non-canonical mechanism of GPCR activation.Nature communications · 2024Article
- GLP-1 Receptor Agonists: A Promising Therapy for Modern Lifestyle Diseases with Unforeseen Challenges.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of Small-Molecule Antagonists Targeting the Growth Hormone Releasing Hormone Receptor (GHRHR).Journal of chemical information and modeling · 2024Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are members of the secretin-like class B family of G-protein-coupled receptors (GPCRs) and have opposing physiological roles in insulin release and glucose homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP-1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose-dependent manner. Here we report crystal structures of the human GLP-1R transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 Å resolution, respectively. The structures reveal a common binding pocket for negative allosteric modulators, present in both GLP-1R and GCGR and located outside helices V-VII near the intracellular half of the receptor. The receptor is in an inactive conformation with compounds that restrict movement of the intracellular tip of helix VI, a movement that is generally associated with activation mechanisms in class A GPCRs. Molecular modelling and mutagenesis studies indicate that agonist positive allosteric modulators target the same general region, but in a distinct sub-pocket at the interface between helices V and VI, which may facilitate the formation of an intracellular binding site that enhances G-protein coupling.
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.