Structural Basis for Voltage Gating and Dalfampridine Binding in the Shaker Potassium Channel.

ABSTRACT: The generation and propagation of action potentials in neurons depend on the coordinated activation of voltage-dependent sodium and potassium channels. Potassium channels of the Shaker family regulate neuronal excitability through voltage-dependent opening and closing of their ion conduction pore. This family of channels is an important therapeutic target, particularly in multiple sclerosis where the inhibitor dalfampridine (4-aminopyridine) is used to improve nerve conduction. The molecular details of how the voltage sensor domain drives opening of the pore domain has been limited by the lack of closed-state structures, also impairing the search for novel drugs. Using AlphaFold2-based conformational sampling methods we identify a structural model for the closed Shaker potassium channel wh

SUBMITTER: Pinto-Anwandter BI 

PROVIDER: S-EPMC11526897 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature