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Open data
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Basic information
Entry | Database: PDB / ID: 8wkw | ||||||
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Title | Structure of MAVS-CARD Filament | ||||||
![]() | Mitochondrial antiviral-signaling protein | ||||||
![]() | IMMUNE SYSTEM / Filament | ||||||
Function / homology | ![]() positive regulation of IP-10 production / regulation of peroxisome organization / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / protein localization to mitochondrion / positive regulation of type I interferon-mediated signaling pathway / peroxisomal membrane ...positive regulation of IP-10 production / regulation of peroxisome organization / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / protein localization to mitochondrion / positive regulation of type I interferon-mediated signaling pathway / peroxisomal membrane / TRAF6 mediated IRF7 activation / negative regulation of viral genome replication / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / cellular response to exogenous dsRNA / positive regulation of NLRP3 inflammasome complex assembly / TRAF6 mediated NF-kB activation / positive regulation of interferon-alpha production / positive regulation of type I interferon production / ubiquitin ligase complex / positive regulation of defense response to virus by host / signaling adaptor activity / antiviral innate immune response / activation of innate immune response / protein serine/threonine kinase binding / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / Negative regulators of DDX58/IFIH1 signaling / molecular condensate scaffold activity / mitochondrial membrane / PKR-mediated signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Evasion by RSV of host interferon responses / positive regulation of interleukin-6 production / positive regulation of protein import into nucleus / positive regulation of tumor necrosis factor production / SARS-CoV-1 activates/modulates innate immune responses / Ovarian tumor domain proteases / TRAF3-dependent IRF activation pathway / protein-macromolecule adaptor activity / molecular adaptor activity / defense response to virus / DNA-binding transcription factor binding / mitochondrial outer membrane / positive regulation of canonical NF-kappaB signal transduction / intracellular signal transduction / defense response to bacterium / innate immune response / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / identical protein binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.21 Å | ||||||
![]() | Shi, M. / Gao, P. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Nucleic-acid-induced ZCCHC3 condensation promotes broad innate immune responses. Authors: Miao Shi / Tao Jiang / Mengfan Zhang / Quanjin Li / Kexin Liu / Ni Lin / Xinlu Wang / Amin Jiang / Yina Gao / Yong Wang / Songqing Liu / Liguo Zhang / Dong Li / Pu Gao / ![]() Abstract: Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and cyclic GMP-AMP synthase (cGAS) recognize aberrant nucleic acids and initiate antiviral responses. Host factor zinc finger CCHC domain- ...Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and cyclic GMP-AMP synthase (cGAS) recognize aberrant nucleic acids and initiate antiviral responses. Host factor zinc finger CCHC domain-containing protein 3 (ZCCHC3) positively regulates both RLRs- and cGAS-mediated signaling through unknown mechanisms. Here, we show that ZCCHC3 employs a broad and unified strategy to promote these pathways in human cell lines. Rather than developing strong protein-protein interactions, ZCCHC3 harbors multiple nucleic-acid-binding modules and undergoes robust liquid phase condensation with nucleic acids. RNA-induced ZCCHC3 condensates enrich and activate RLRs, which then facilitate the interaction of RLRs with the downstream adaptor mitochondrial antiviral-signaling (MAVS). Direct and high-resolution structure determination of liquid condensates confirms the assembly of active-form MAVS filaments. Furthermore, ZCCHC3 efficiently promotes the condensation and enrichment of DNA, cGAS, ATP, and GTP, thereby enhancing cGAS signaling. ZCCHC3 mutants defective in RNA/DNA-induced condensation lost their regulatory efficiency in both pathways. These results highlight unexpectedly broad connections between biomolecular condensation and innate immunity. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 590.3 KB | Display | ![]() |
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PDB format | ![]() | 473 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 53.2 KB | Display | |
Data in CIF | ![]() | 84.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 37609MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 11327.857 Da / Num. of mol.: 26 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Has protein modification | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: MAVS-CARD / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
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
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
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
EM software | Name: PHENIX / Version: 1.19.2_4158: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80454 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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