ArticleNature communications2022
Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Insulin mimetics and non-canonical insulin receptor signaling: mechanisms and disease relevance.Experimental & molecular medicine · 2026Review
- Nucleic acid aptamers: new methods for selection, target validation, molecular diagnostics and therapeutics.Signal transduction and targeted therapy · 2026Review
- Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2.Nature communications · 2026Article
- Discovery and Cryo-EM-Guided Development of a Neuropilin-2-Binding Aptamer for Receptor Antagonism.Journal of the American Chemical Society · 2026Article
- Expedient single-round selection of hyper-modified aptamer targeting insulin receptor from over-represented dually nucleobase-modified DNA libraries.Nature communications · 2026Article
- CD25-Targeted Aptamer-Drug Conjugate for the Treatment of CD25-Expressing Hematological Malignancies.Pharmaceutics · 2026Article
- Expanded genetic alphabet increases structural and chemical diversity of six-letter DNA for high-affinity protein-targeting aptamers.Nature communications · 2025Article
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.Pharmaceutics · 2025Review
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.Biochemistry · 2024Article
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.bioRxiv : the preprint server for biology · 2024Article
- Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions.Nature communications · 2024Article
- A λ-Dynamics Investigation of InsulinJournal of chemical information and modeling · 2024Article
- A λ-dynamics investigation of insulinbioRxiv : the preprint server for biology · 2024Article
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- UCSF ChimeraX: Tools for structure building and analysis.Protein science : a publication of the Protein Society · 2023Article
- Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.Nature communications · 2023Article
- A stepwise activation model for the insulin receptor.Experimental & molecular medicine · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2' insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains.
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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.