ZBP1 specifically binds pre-formed Z-RNA, limiting its potential pool of nucleic acid ligands compared to ADAR1.

ZBP1's Zα domains specifically bind pre-formed Z-RNA and cannot flip unmodified dsRNA into the Z-conformation, unlike ADAR1's Zα domain.

• Why it matters: Understanding the distinct binding capabilities of ZBP1 and ADAR1 is crucial for elucidating their roles in immune responses and cell fate decisions during infection and disease.
• What they did: The study used NMR and biochemical experiments to analyze ZBP1's Zα1 and Zα2 domains, revealing that they require chemically modified dsRNA to bind and stabilize Z-conformation, and cannot flip unmodified dsRNA.
• The result: These findings suggest ZBP1 limits its nucleic acid ligand pool to pre-formed Z-RNA, which may influence its function in infection and disease, and highlight differences from ADAR1's broader substrate recognition.