8WKW

Structure of MAVS-CARD Filament

Summary for 8WKW

• Entry DOI: 10.2210/pdb8wkw/pdb
• EMDB information: 37609
• Descriptor: Mitochondrial antiviral-signaling protein (1 entity in total)
• Functional Keywords: filament, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 26
• Total formula weight: 294524.28

Authors

Shi, M.,Gao, P. (deposition date: 2023-09-28, release date: 2024-10-16, Last modification date: 2025-04-30)

Primary citation

Shi, M.,Jiang, T.,Zhang, M.,Li, Q.,Liu, K.,Lin, N.,Wang, X.,Jiang, A.,Gao, Y.,Wang, Y.,Liu, S.,Zhang, L.,Li, D.,Gao, P.
Nucleic-acid-induced ZCCHC3 condensation promotes broad innate immune responses.
Mol.Cell, 85:962-975.e7, 2025

PubMed 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-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.

PubMed: 39983719
DOI: 10.1016/j.molcel.2025.01.027

Experimental method

ELECTRON MICROSCOPY (3.21 Å)