ArticleThe Journal of cell biology2020
Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed.
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- Ligand regulation and function of preformed EGFR dimers.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2.Nature communications · 2026Article
- Reprogramming insulin receptor activation with a de novo agonist to overcome severe insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Evolution of Insulin, Insulin-like Growth Factors, and Their Cognate Receptors in Vertebrates, Invertebrates, and Viruses.Molecular biology and evolution · 2026Article
- Article
- Tuning insulin receptor signaling using de novo-designed agonists.Molecular cell · 2025Article
- Structure and activation of the Drosophila insulin receptor by three Drosophila insulin-like peptides.Nature communications · 2025Article
- Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance.Nature communications · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Multiscale Computational Protocols for Accurate Residue Interactions at the Flexible Insulin-Receptor Interface.Journal of chemical information and modeling · 2025Article
- The use of intuitive AF-based modelling for the understanding of activation and signalling through insulin-like receptors.Frontiers in endocrinology · 2025Review
- Recent Applications of In Silico Approaches for Studying Receptor Mutations Associated with Human Pathologies.Molecules (Basel, Switzerland) · 2024Review
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.Biochemistry · 2024Article
- Article
- Molecular Aspects in the Development of Type 2 Diabetes and Possible Preventive and Complementary Therapies.International journal of molecular sciences · 2024Review
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.bioRxiv : the preprint server for biology · 2024Article
- A λ-Dynamics Investigation of InsulinJournal of chemical information and modeling · 2024Article
- Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain.Molecular pharmaceutics · 2024Article
- Activation of the insulin receptor by insulin-like growth factor 2.Nature communications · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design.
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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.