A carboxy-terminal inter-helix linker as the site of phosphatidylinositol 4,5-bisphosphate action on Kv7 (M-type) K+ channels.

ABSTRACT: The regulation of M-type (KCNQ [Kv7]) K(+) channels by phosphatidylinositol 4,5-bisphosphate (PIP(2)) has perhaps the best correspondence to physiological signaling, but the site of action and structural motif of PIP(2) on these channels have not been established. Using single-channel recordings of chimeras of Kv7.3 and 7.4 channels with highly differential PIP(2) sensitivities, we localized a carboxy-terminal inter-helix linker as the primary site of PIP(2) action. Point mutants within this linker in Kv7.2 and Kv7.3 identified a conserved cluster of basic residues that interact with the lipid using electrostatic and hydrogen bonds. Homology modeling of this putative PIP(2)-binding linker in Kv7.2 and Kv7.3 using the solved structure of Kir2.1 and Kir3.1 channels as templates predicts a st

SUBMITTER: Hernandez CC 

PROVIDER: S-EPMC2518730 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature