ArticleThe Journal of biological chemistry2014
Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- ThebioRxiv : the preprint server for biology · 2026Article
- Importance of the inflammasome in gut-brain axis: from pathological driver to therapeutic target.Inflammopharmacology · 2026Review
- Familial Mediterranean Fever: A Comprehensive Review of Pathogenesis, Genetics, and Epigenetic Regulation.Balkan medical journal · 2026Review
- NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives.RSC medicinal chemistry · 2025Review
- Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Familial Mediterranean fever gene variations could triggerRheumatology advances in practice · 2024Article
- Nanoscale organization of the endogenous ASC speck.iScience · 2023Article
- TRIMs: Generalists Regulating the NLRP3 Inflammasome Signaling Pathway.DNA and cell biology · 2022Review
- The pyrin inflammasome and the Yersinia effector interaction.Immunological reviews · 2020Review
- Inflammasome activation and regulation: toward a better understanding of complex mechanisms.Cell discovery · 2020Review
- Structure, interactions and self-assembly of ASC-dependent inflammasomes.Archives of biochemistry and biophysics · 2019Review
- Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes.Rheumatology international · 2018Article
- Intracellular Antiviral Immunity.Advances in virus research · 2018Review
- Transmissible gastroenteritis virus infection induces NF-κB activation through RLR-mediated signaling.Virology · 2017Article
- Assembly and regulation of ASC specks.Cellular and molecular life sciences : CMLS · 2017Review
- Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout.Scientific reports · 2016Article
- ASC Pyrin Domain Self-associates and Binds NLRP3 Protein Using Equivalent Binding Interfaces.The Journal of biological chemistry · 2016Article
- Update on Pyrin Functions and Mechanisms of Familial Mediterranean Fever.Frontiers in microbiology · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammasomes are macromolecular complexes that mediate inflammatory and cell death responses to pathogens and cellular stress signals. Dysregulated inflammasome activation is associated with autoinflammatory syndromes and several common diseases. During inflammasome assembly, oligomerized cytosolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC. Inflammasome assembly is mediated by pyrin domains (PYDs) and caspase recruitment domains, which are protein interaction domains of the death fold superfamily. However, the molecular details of their interactions are poorly understood. We have studied the interaction between ASC and pyrin PYDs that mediates ASC recruitment to the pyrin inflammasome, which is implicated in the pathogenesis of familial Mediterranean fever. We demonstrate that both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD. Molecular docking of pyrin-ASC PYD complexes showed that pyrin PYD can simultaneously interact with up to three ASC PYDs. Furthermore, ASC PYD can self-associate and interact with pyrin, consistent with previous reports that pyrin promotes ASC clustering to form a proinflammatory complex. Finally, the effects of familial Mediterranean fever-associated mutations, R42W and A89T, on structural and functional properties of pyrin PYD were investigated. The R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC, it also bound less to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active. Our data give new insights into the binding modes of PYDs and inflammasome architecture.
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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.