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- PDB-8wkw: Structure of MAVS-CARD Filament -

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Basic information

Entry
Database: PDB / ID: 8wkw
TitleStructure of MAVS-CARD Filament
ComponentsMitochondrial antiviral-signaling protein
KeywordsIMMUNE SYSTEM / Filament
Function / homology
Function and homology information


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
IPS1, CARD domain / : / Caspase recruitment domain / Caspase recruitment domain / Death-like domain superfamily
Similarity search - Domain/homology
Mitochondrial antiviral-signaling protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.21 Å
AuthorsShi, M. / Gao, P.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32130057, 31922037, 81921005, 32271275 China
CitationJournal: Mol Cell / Year: 2025
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
DepositionSep 28, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 1.1Apr 30, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Mitochondrial antiviral-signaling protein
B: Mitochondrial antiviral-signaling protein
C: Mitochondrial antiviral-signaling protein
D: Mitochondrial antiviral-signaling protein
E: Mitochondrial antiviral-signaling protein
F: Mitochondrial antiviral-signaling protein
G: Mitochondrial antiviral-signaling protein
H: Mitochondrial antiviral-signaling protein
I: Mitochondrial antiviral-signaling protein
J: Mitochondrial antiviral-signaling protein
K: Mitochondrial antiviral-signaling protein
L: Mitochondrial antiviral-signaling protein
M: Mitochondrial antiviral-signaling protein
N: Mitochondrial antiviral-signaling protein
O: Mitochondrial antiviral-signaling protein
P: Mitochondrial antiviral-signaling protein
Q: Mitochondrial antiviral-signaling protein
R: Mitochondrial antiviral-signaling protein
S: Mitochondrial antiviral-signaling protein
T: Mitochondrial antiviral-signaling protein
U: Mitochondrial antiviral-signaling protein
V: Mitochondrial antiviral-signaling protein
W: Mitochondrial antiviral-signaling protein
X: Mitochondrial antiviral-signaling protein
Y: Mitochondrial antiviral-signaling protein
Z: Mitochondrial antiviral-signaling protein


Theoretical massNumber of molelcules
Total (without water)294,52426
Polymers294,52426
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein ...
Mitochondrial antiviral-signaling protein


Mass: 11327.857 Da / Num. of mol.: 26
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAVS / Production host: Escherichia coli (E. coli) / References: UniProt: Q7Z434
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: MAVS-CARD / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.19.2_4158: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80454 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00221112
ELECTRON MICROSCOPYf_angle_d0.42728730
ELECTRON MICROSCOPYf_dihedral_angle_d3.4172860
ELECTRON MICROSCOPYf_chiral_restr0.0363146
ELECTRON MICROSCOPYf_plane_restr0.0033718

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