ArticleNature communications2023
Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.Biomolecules · 2026Review
- Cryo-EM structure of the interleukin-31 receptor complex defines non-canonical interactions that confer receptor specificity.The Journal of biological chemistry · 2026Article
- Gαi1 and Gαi3 mediate IL-11-induced signal transduction and are potential therapeutic targets for LUAD.Cell death & disease · 2026Article
- The role of IL-11 in chronic diseases.Frontiers in immunology · 2026Review
- Triple-Negative Breast Cancer Cells Resist Natural Killer Cell-Mediated Killing Through Interleukin-11 Trans-Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Investigating plasticity within the interleukin-6 family with AlphaFold-Multimer.Computational and structural biotechnology journal · 2025Article
- PDK2-enhanced glycolysis aggravates fibrosis via IL11 signaling pathway in Graves' orbitopathy.Frontiers in immunology · 2025Article
- Targeting the major pro-inflammatory interleukin-6-type cytokine receptor gp130 by antagonistic single domain antibodies.Frontiers in immunology · 2025Article
- Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes.Nature communications · 2024Article
- Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency.Nature communications · 2024Article
- Structural insights into the assembly of gp130 family cytokine signaling complexes.Science advances · 2023Article
- Therapeutic targets for fibro-inflammation in Graves' orbitopathy.Taiwan journal of ophthalmologyReview
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family β-receptor, gp130. We show that complex formation requires conformational reorganisation of IL-11 and that the membrane-proximal domains of gp130 are dynamic. We demonstrate that the cytokine mutant, IL-11 Mutein, competitively inhibits signalling in human cell lines. Structural shifts in IL-11 Mutein underlie inhibition by altering cytokine binding interactions at all three receptor-engaging sites and abrogating the final gp130 binding step. Our results reveal the structural basis of IL-11 signalling, define the molecular mechanisms of an inhibitor, and advance understanding of gp130-containing receptor complexes, with potential applications in therapeutic development.
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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.