ArticleProceedings of the National Academy of Sciences of the United States of America2006
Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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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.
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Who cites it
135 citing papers in PubMed, 278 citations in OpenAlex.
- TransCon IL-2 β/γ: a novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer.Journal for immunotherapy of cancer · 2022Trial
- Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease.Science translational medicine · 2013Trial
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Messenger RNA delivery of a dual CD25/CD122 affinity-tuned IL-2 variant prolongs exposure and potentiates antitumor T cell immunity.Science advances · 2026Article
- A Tumor-Microenvironment-Responsive Chemically Masked IL‑2 Prodrug Potentiates PD‑1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy.ACS central science · 2026Article
- Engineered iMSCs delivering wild-type IL-2 achieve dose-sparing tumor control via CD25-dependent CD8BMC medicine · 2026Article
- Transcriptional signatures of rapid protection from Sudan virus infection by a single dose of a vesicular stomatitis virus-based vaccine.PLoS pathogens · 2026Article
- Article
- Cytokines Associated with Activation of CD4International journal of molecular sciences · 2026Review
- Advances in IL-2-based cancer immunotherapy and the synergistic role of stem-like CD8Frontiers in immunology · 2026Review
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells.The Journal of veterinary medical science · 2025Article
- A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management.Journal of proteome research · 2025Review
- Reshape the Fates of Treg and CD8+T Cells Through IL-2Rα by Synergizing Divergent Receptor-Biased IL-2 PEGylates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- IL-2Rα is dispensable for murine B cell development and humoral response.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Enhancing the Anticancer Activity of a Carcinoma-Directed Peptide-HLA-I Fusion Protein by Armoring with Mutein IFNα.International journal of molecular sciences · 2025Article
- Regulating IL-2 Immune Signaling Function Via A Core Allosteric Structural Network.Journal of molecular biology · 2025Article
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Directed disruption of IL2 aggregation and receptor binding sites produces designer biologics with enhanced specificity and improved production capacity.Computational and structural biotechnology journal · 2025Article
- SHR-1916: A Novel PEGylated Interleukin-2 Analogue with Altered Cellular Selectivity and Improved Pharmacokinetic Profiles for Cancer Immunotherapy.Drug design, development and therapy · 2025Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits IL-2R alpha, IL-2R beta, and gamma(c). Here, we describe the crystal structure of the trimeric assembly of the human IL-2 receptor ectodomains in complex with IL-2 at 3.0 A resolution. The quaternary structure is consistent with a stepwise assembly from IL-2/IL-2R alpha to IL-2/IL-2R alpha/IL-2R beta to IL-2/IL-2R alpha/IL-2R beta/gamma(c). The IL-2R alpha subunit forms the largest of the three IL-2/IL-2R interfaces, which, together with the high abundance of charge-charge interactions, correlates well with the rapid association rate and high-affinity interaction of IL-2R alpha with IL-2 at the cell surface. Surprisingly, IL-2R alpha makes no contacts with IL-2R beta or gamma(c), and only minor changes are observed in the IL-2 structure in response to receptor binding. These findings support the principal role of IL-2R alpha to deliver IL-2 to the signaling complex and act as regulator of signal transduction. Cooperativity in assembly of the final quaternary complex is easily explained by the extraordinarily extensive set of interfaces found within the fully assembled IL-2 signaling complex, which nearly span the entire length of the IL-2R beta and gamma(c) subunits. Helix A of IL-2 wedges tightly between IL-2R beta and gamma(c) to form a three-way junction that coalesces into a composite binding site for the final gamma(c) recruitment. The IL-2/gamma(c) interface itself exhibits the smallest buried surface and the fewest hydrogen bonds in the complex, which is consistent with its promiscuous use in other cytokine receptor complexes.
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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.