How does propofol binding at the S5-S6 interface stabilize voltage sensor-pore coupling without affecting voltage sensor movement?

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Description

The study shows propofol inhibition is independent of voltage-sensor conformational changes, yet somehow stabilizes coupling between voltage sensor and pore. The molecular mechanism of this allosteric coupling stabilization remains unexplained.

Gap type: unexplained_observation Source paper: Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. (2024, Nature, PMID:39085604)

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