9OJV

Crystal structure of monoclonal J2 antibody bound to dsRNA

Summary for 9OJV

• Entry DOI: 10.2210/pdb9ojv/pdb
• Descriptor: J2 Fab heavy chain, J2 Fab light chain, RNA strand1, ... (6 entities in total)
• Functional Keywords: antibody dsrna j2 antibody double-stranded rna fab fragment antigen-binding region, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 6
• Total formula weight: 113562.40

Authors

Bou-Nader, C.,Zhang, J. (deposition date: 2025-05-08, release date: 2025-12-10, Last modification date: 2026-03-25)

Primary citation

Bou-Nader, C.,Juma, K.M.,Bothra, A.,Brasington, A.J.,Ghirlando, R.,Suzuki, M.,Garboczi, D.N.,Leppla, S.H.,Zhang, J.
Structural basis of double-stranded RNA recognition by the J2 monoclonal antibody.
Nat Commun, 17:635-635, 2025

PubMed Abstract: Double-stranded (ds) RNAs are major structural components of the transcriptome, hallmarks of viral infection, and primary triggers of innate immune responses. The J2 monoclonal antibody is the gold-standard method to discover and map endogenous dsRNAs across subcellular locations and cell surfaces, detect exogenous RNAs in viral infection, and surveil mRNA prophylactics and therapeutics for inflammatory dsRNAs. To define its epitope, specificity, and mechanism, we determine a 2.85 Å co-crystal structure of J2 antigen-binding fragment (Fab) bound to dsRNA. J2 uses its heavy and light chains in tandem to track the dsRNA minor groove, recognizing a staggered 8-bp duplex. J2 is highly selective for dsRNAs, requires 14 bp for robust binding, and exhibits greatly diminished binding for GC-rich dsRNAs. J2 and the R-loop-specific S9.6 antibody share a common recognition strategy distinct from intracellular dsRNA-binding proteins. This study provides mechanistic insights into dsRNA recognition and establishes a framework for reliable application and data interpretation of the J2 antibody in RNA discovery.

PubMed: 41390480
DOI: 10.1038/s41467-025-67414-z

Experimental method

X-RAY DIFFRACTION (2.85 Å)