Structure of the voltage-gated potassium channel K_V1.3: Insights into the inactivated conformation and binding to therapeutic leads.

ABSTRACT: The voltage-gated potassium channel K_V1.3 is an important therapeutic target for the treatment of autoimmune and neuroinflammatory diseases. The recent structures of K_V1.3, Shaker-IR (wild-type and inactivating W434F mutant) and an inactivating mutant of rat K_V1.2-K_V2.1 paddle chimera (K_VChim-W362F+S367T+V377T) reveal that the transition of voltage-gated potassium channels from the open-conducting conformation into the non-conducting inactivated conformation involves the rupture of a key intra-subunit hydrogen bond that tethers the selectivity filter to the pore helix. Breakage of this bond allows the side chains of residues at the external end of the selectivity filter (Tyr447 and Asp449 in K_V1.3) to rotate outwards, dilati

SUBMITTER: Chandy KG 

PROVIDER: S-EPMC10496531 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature