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Open data
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Basic information
| Entry | Database: PDB / ID: 9u8k | ||||||||||||||||||||||||
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| Title | Structure of ASC-PYD filament from condensates | ||||||||||||||||||||||||
Components | Apoptosis-associated speck-like protein containing a CARD | ||||||||||||||||||||||||
Keywords | IMMUNE SYSTEM / ASC-PYD / filament / condensates | ||||||||||||||||||||||||
| Function / homology | Function and homology informationCLEC7A/inflammasome pathway / The NLRP3 inflammasome / peptidase activator activity involved in apoptotic process / NLRP6 inflammasome complex / myosin I binding / Pyrin domain binding / myeloid dendritic cell activation involved in immune response / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / regulation of intrinsic apoptotic signaling pathway / myeloid dendritic cell activation ...CLEC7A/inflammasome pathway / The NLRP3 inflammasome / peptidase activator activity involved in apoptotic process / NLRP6 inflammasome complex / myosin I binding / Pyrin domain binding / myeloid dendritic cell activation involved in immune response / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / regulation of intrinsic apoptotic signaling pathway / myeloid dendritic cell activation / IkappaB kinase complex / AIM2 inflammasome complex / NLRP1 inflammasome complex / macropinocytosis / canonical inflammasome complex / interleukin-6 receptor binding / BMP receptor binding / NLRP3 inflammasome complex / NLRP3 inflammasome complex assembly / positive regulation of adaptive immune response / cysteine-type endopeptidase activator activity / negative regulation of interferon-beta production / regulation of tumor necrosis factor-mediated signaling pathway / regulation of GTPase activity / osmosensory signaling pathway / positive regulation of activated T cell proliferation / positive regulation of extrinsic apoptotic signaling pathway / pattern recognition receptor signaling pathway / pattern recognition receptor activity / tropomyosin binding / positive regulation of actin filament polymerization / positive regulation of release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway by p53 class mediator / positive regulation of interleukin-10 production / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / pyroptotic inflammatory response / cellular response to interleukin-1 / positive regulation of T cell migration / positive regulation of defense response to virus by host / positive regulation of chemokine production / Neutrophil degranulation / negative regulation of cytokine production involved in inflammatory response / activation of innate immune response / intrinsic apoptotic signaling pathway / positive regulation of phagocytosis / tumor necrosis factor-mediated signaling pathway / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / negative regulation of canonical NF-kappaB signal transduction / response to bacterium / apoptotic signaling pathway / regulation of protein stability / positive regulation of non-canonical NF-kappaB signal transduction / protein homooligomerization / positive regulation of interleukin-6 production / positive regulation of JNK cascade / cellular response to tumor necrosis factor / positive regulation of type II interferon production / positive regulation of T cell activation / positive regulation of tumor necrosis factor production / positive regulation of inflammatory response / cellular response to lipopolysaccharide / regulation of inflammatory response / protease binding / regulation of apoptotic process / defense response to virus / defense response to Gram-negative bacterium / microtubule / transmembrane transporter binding / positive regulation of canonical NF-kappaB signal transduction / positive regulation of ERK1 and ERK2 cascade / protein dimerization activity / defense response to Gram-positive bacterium / positive regulation of apoptotic process / inflammatory response / Golgi membrane / innate immune response / neuronal cell body / apoptotic process / nucleolus / enzyme binding / endoplasmic reticulum / protein homodimerization activity / protein-containing complex / mitochondrion / extracellular region / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||
| Biological species | human gammaherpesvirus 4 (Epstein-Barr virus) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||||||||||||||||||||
Authors | Gao, P. / Li, Q.J. / Li, Z.L. | ||||||||||||||||||||||||
| Funding support | 1items
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Citation | Journal: Protein Cell / Year: 2026Title: DNA-triggered AIM2 condensation orchestrates immune activation and regulation. Authors: Quanjin Li / Xiaohan Geng / Huiwen Yan / Zhaolong Li / Miao Shi / Ziqi Zhu / Tongxin Niu / Chunqiu Zhao / Kaile Shu / Yina Gao / Han Feng / Songqing Liu / Qiuyao Jiang / Pengcheng Bu / Dong Li / Pu Gao / ![]() Abstract: 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 ...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. | ||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9u8k.cif.gz | 573.2 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9u8k.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9u8k.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u8/9u8k ftp://data.pdbj.org/pub/pdb/validation_reports/u8/9u8k | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 63955MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 11547.250 Da / Num. of mol.: 39 Source method: isolated from a genetically manipulated source Source: (gene. exp.) human gammaherpesvirus 4 (Epstein-Barr virus)Production host: ![]() Has protein modification | N | |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: ASC-PYD filament from condensates / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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| Source (natural) | Organism: Epstein-Barr virus (strain GD1) (Epstein-Barr virus) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Microscopy | Model: TFS TITAN THEMIS |
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| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
| 3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45400 / Symmetry type: POINT |
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human gammaherpesvirus 4 (Epstein-Barr virus)
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FIELD EMISSION GUN