Academic Journal
DNA-triggered AIM2 condensation orchestrates immune activation and regulation.
| Τίτλος: | DNA-triggered AIM2 condensation orchestrates immune activation and regulation. |
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| Συγγραφείς: | Li Q; School of Life Science, Beijing Institute of Technology, Beijing 100081, China.; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Geng X; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Yan H; State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Li Z; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Shi M; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China., Zhu Z; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Niu T; Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Zhao C; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Shu K; University of Chinese Academy of Sciences, Beijing 100049, China.; State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Gao Y; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Feng H; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Liu S; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Jiang Q; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China., Bu P; University of Chinese Academy of Sciences, Beijing 100049, China.; State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Li D; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China.; State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, IDG/McGovern Institute for Brain Research, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China., Gao P; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China.; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China. |
| Πηγή: | Protein & cell [Protein Cell] 2026 Sep 01; Vol. 17 (9), pp. 807-820. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: Germany NLM ID: 101532368 Publication Model: Print Cited Medium: Internet ISSN: 1674-8018 (Electronic) Linking ISSN: 1674800X NLM ISO Abbreviation: Protein Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : [Oxford] : Oxford University Press Original Publication: Heidelberg : Beijing, China : Springer ; Higher Education Press |
| Ιατρικοί όροι (MeSH): | DNA-Binding Proteins*/immunology , DNA-Binding Proteins*/chemistry , DNA-Binding Proteins*/genetics , DNA-Binding Proteins*/metabolism , Inflammasomes*/immunology , Inflammasomes*/metabolism , DNA*/immunology , DNA*/chemistry , DNA*/metabolism , Immunity, Innate*, Animals ; Humans ; Innate Immunity Recognition ; Mice ; Phase Separation |
| Περίληψη: | The innate immune sensor AIM2 detects cytosolic DNA and initiates inflammatory responses, yet its activation mechanism remains incompletely understood. Here, we show that AIM2 undergoes liquid-liquid phase separation upon DNA binding, forming dynamic condensates both in vitro and in cells. These condensates serve as platforms for inflammasome and PANoptosome assembly, promoting immune activation across multiple pathways. Direct structural determination from condensates reveals the assembly of active-form ASC filaments. Mechanistically, liquid-phase condensation is governed by multivalent interactions involving different AIM2 domains, including previously uncharacterized regions and species-specific elements. In vitro and in vivo assays show that mutants specifically disrupting condensation impair immune complex assembly, cell death initiation, antimicrobial defense, and intestinal homeostasis. Moreover, AIM2-DNA condensates function as regulatory hubs targeted by host- and pathogen-derived factors to balance immune homeostasis or facilitate immune evasion. These findings establish liquid-phase condensation as a fundamental mechanism of AIM2 activation and a potential therapeutic target. (© The Author(s) 2026. Published by Oxford University Press on behalf of Higher Education Press.) |
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| Grant Information: | 2025ZD01904303 National Science and Technology Major Project of China; 32325028 National Natural Science Foundation of China; 32130057 National Natural Science Foundation of China; 32571417 National Natural Science Foundation of China; 2024YFA1307400 National Key R&D Program of China; XDB1310000 Strategic Priority Research Program; Z220018 Beijing Natural Science Foundation; JZHKYPT-2021-05 Basic Research Program Based on Major Scientific Infrastructures-CAS; YSBR-074 CAS Project for Young Scientists in Basic Research |
| Contributed Indexing: | Keywords: AIM2; PANoptosome; inflammasome; innate immune; phase separation |
| Substance Nomenclature: | 0 (DNA-Binding Proteins) 0 (AIM2 protein, human) 0 (Inflammasomes) 9007-49-2 (DNA) 0 (Aim2 protein, mouse) |
| Entry Date(s): | Date Created: 20260326 Date Completed: 20260827 Latest Revision: 20260923 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13521274 |
| DOI: | 10.1093/procel/pwag024 |
| PMID: | 41883156 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1674-8018 |
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| DOI: | 10.1093/procel/pwag024 |