Tandem RNA-binding domain architecture drives PKR activation through an intramolecular interface.

Tandem dsRNA-binding domains in PKR form a unique intramolecular interface essential for activating immune responses, with disruption impairing function.

• Why it matters: Understanding how RNA-binding proteins like PKR regulate immune signaling is crucial, as their structural arrangements influence their ability to detect viral RNAs and trigger defenses.
• What they did: Researchers used structural and functional analyses to show that PKR’s two dsRNA-binding domains assemble via an intramolecular interface, stabilizing RNA binding and enabling downstream activation.
• The result: Disrupting the dsRBD1:dsRBD2 interface dismantles PKR’s architecture and severely reduces its activity, highlighting intramolecular coupling as a key regulatory mechanism for RBP function.