Oxidation of NADPH on Kvbeta1 inhibits ball-and-chain type inactivation by restraining the chain.

ABSTRACT: The Kv1 family voltage-dependent K(+) channels assemble with cytosolic ? subunits (Kv?), which are composed of a flexible N terminus followed by a structured core domain. The N terminus of certain Kv?s inactivates the channel by blocking the ion conduction pore, and the core domain is a functional enzyme that uses NADPH as a cofactor. Oxidation of the Kv?-bound NADPH inhibits inactivation and potentiates channel current, but the mechanism behind this effect is unknown. Here we show that after oxidation, the core domain binds to part of the N terminus, thus restraining it from blocking the channel. The interaction is partially mediated by two negatively charged residues on the core domain and three positively charged ones on the N terminus. These results provide a molecular basis for the coupling between the cellular redox state and channel activity, and establish Kv? as a target for pharmacological control of Kv1 channels.

SUBMITTER: Pan Y 

PROVIDER: S-EPMC3078402 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature