Enterovirus 2B protein: From viroporin to membrane stress sensor, mechanistic principles of multi-pathway regulation.

Enterovirus 2B functions as a membrane stress sensor regulating multiple cell death pathways, beyond its traditional role as an ion channel, with conformational dynamics influencing calcium signaling and immune evasion.

• Why it matters: Understanding 2B's diverse roles is crucial because its interactions with host factors and functional divergence among enteroviruses are not explained by the classic viroporin model, limiting antiviral strategies.
• What they did: The study proposes a novel membrane stress sensor hypothesis, supported by structure-function mapping, calcium signaling, and immune evasion analyses, across six key dimensions, including evolutionary and antiviral aspects.
• The result: This framework advances mechanistic insights into 2B's multifunctionality and provides a foundation for developing targeted anti-enteroviral therapies.