Voltage gating and 4-aminopyridine inhibition in the Shaker Kv channel revealed by a closed-state model.

ABSTRACT: The generation and propagation of action potentials in neurons relies on the coordinated activation of voltage-dependent sodium and potassium channels. The Kv1 (Shaker) family of potassium channels drives the repolarization phase of the action potential by opening and closing their pore, a process controlled by a voltage sensor domain. However, a molecular description of how the voltage sensor domain drives pore gating has been constrained by a lack of closed-state structures. Here, we present a structural model of the closed Shaker channel that reveals the structural basis of voltage gating. Using AlphaFold2-based conformational sampling, we identified a partially activated state of the voltage sensor which, when modeled with the full channel, produced a closed state. Based on this model

SUBMITTER: Pinto-Anwandter BI 

PROVIDER: S-EPMC12392982 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature