ArticleStructure (London, England : 1993)2021
Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation.
Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 34 citations in OpenAlex.
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- Integrated analysis of bioinformatics, mendelian randomization, and experimental validation reveals novel diagnostic and therapeutic targets for osteoarthritis: progesterone as a potential therapeutic agent.Journal of orthopaedic surgery and research · 2025Article
- IRAK3 is upregulated in rheumatoid arthritis synovium and delays the onset of experimental arthritis.Frontiers in immunology · 2025Article
- Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance.Journal of autoimmunity · 2024Article
- A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling.Science signaling · 2023Article
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.International journal of molecular sciences · 2023Article
- IL-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy.The Journal of clinical investigation · 2023Article
- The IRAK-M death domain: a tale of three surfaces.Frontiers in molecular biosciences · 2023Article
- Looking lively: emerging principles of pseudokinase signaling.Trends in biochemical sciences · 2022Review
- Kincore: a web resource for structural classification of protein kinases and their inhibitors.Nucleic acids research · 2022Article
- The pseudokinase domain in receptor guanylyl cyclases.Methods in enzymology · 2022Review
- Whole-Genome Analyses Reveal Genomic Characteristics and Selection Signatures of Lincang Humped Cattle at the China-Myanmar Border.Frontiers in genetics · 2022Article
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix.Nature communications · 2021Article
- There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.The Journal of biological chemistryReview
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
Interleukin-1 receptor associated kinases (IRAKs) are key players in innate immune signaling that mediate the host response to pathogens. In contrast to the active kinases IRAK1 and IRAK4, IRAK2 and IRAK3 are pseudokinases lacking catalytic activity and their functions are poorly understood. IRAK3 is thought to be a negative regulator of innate immune signaling and mutations in IRAK3 are associated with asthma and cancer. Here, we report the crystal structure of the human IRAK3 pseudokinase domain in a closed, pseudoactive conformation. IRAK3 dimerizes in a unique way through a head-to-head arrangement not observed in any other kinases. Multiple conserved cysteine residues imply a potential redox control of IRAK3 conformation and dimerization. By analyzing asthma-associated mutations, we identify an evolutionarily conserved surface on IRAK3 that could form an interaction interface with IRAK4, suggesting a model for the negative regulation of IRAK4 by IRAK3.
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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.