Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels.

ABSTRACT: Potassium ion conduction through open potassium channels is essential to control of membrane potentials in all cells. To elucidate the open conformation and hence the mechanism of K+ ion conduction in the classic inward rectifier Kir2.2, we introduced a negative charge (G178D) at the crossing point of the inner helix bundle, the location of ligand-dependent gating. This "forced open" mutation generated channels that were active even in the complete absence of phosphatidylinositol-4,5-bisphosphate (PIP2), an otherwise essential ligand for Kir channel opening. Crystal structures were obtained at a resolution of 3.6 Å without PIP2 bound, or 2.8 Å in complex with PIP2. The latter revealed a slight widening at the helix bundle crossing (HBC) through backbone movement. MD simulations showed that

SUBMITTER: Zangerl-Plessl EM 

PROVIDER: S-EPMC7034095 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature