ArticleJournal of molecular biology2017
Dynamic Modulation of Binding Affinity as a Mechanism for Regulating Interferon Signaling.
Article in Journal of molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Lymphocytes and monocytes undergo swift suppression of IL-10R, IL-6R, and IL-2Rβγ signaling under high concentrations of different cytokines.bioRxiv : the preprint server for biology · 2025Article
- A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.The Journal of experimental medicine · 2025Article
- Structure-function of type I and III interferons.Current opinion in immunology · 2024Review
- Nascent transcription upon interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines.BMC research notes · 2023Article
- Ter-Seq: A high-throughput method to stabilize transient ternary complexes and measure associated kinetics.Protein science : a publication of the Protein Society · 2023Article
- Structural dynamics in the evolution of a bilobed protein scaffold.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Intrinsic dynamics is evolutionarily optimized to enable allosteric behavior.Current opinion in structural biology · 2020Review
- Comparative Analyses of the Conformational Dynamics Between the Soluble and Membrane-Bound Cytokine Receptors.Scientific reports · 2020Article
- Modulation of Toroidal Proteins Dynamics in Favor of Functional Mechanisms upon Ligand Binding.Biophysical journal · 2020Article
- Shared and Unique Features of Human Interferon-Beta and Interferon-Alpha Subtypes.Frontiers in immunology · 2020Review
- Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response.Nature communications · 2019Article
- A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.Nature communications · 2018Article
- Mapping Determinants of Cytokine Signaling via Protein Engineering.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
How structural dynamics affects cytokine signaling is under debate. Here, we investigated the dynamics of the type I interferon (IFN) receptor, IFNAR1, and its effect on signaling upon binding IFN and IFNAR2 using a combination of structure-based mechanistic studies, in situ binding, and gene induction assays. Our study reveals that IFNAR1 flexibility modulates ligand-binding affinity, which, in turn, regulates biological signaling. We identified the hinge sites and key interactions implicated in IFNAR1 inter-subdomain (SD1-SD4) movements. We showed that the predicted cooperative movements are essential to accommodate intermolecular interactions. Engineered disulfide bridges, computationally predicted to interfere with IFNAR1 dynamics, were experimentally confirmed. Notably, introducing disulfide bonds between subdomains SD2 and SD3 modulated IFN binding and activity in accordance with the relative attenuation of cooperative movements with varying distance from the hinge center, whereas locking the SD3-SD4 interface flexibility in favor of an extended conformer increased activity.
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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.