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

Eva Maria Zangerl-Plessl, Sun Joo Lee, Grigory Maksaev, Harald Bernsteiner, Feifei Ren, Peng Yuan, Anna Stary-Weinzinger, Colin G. Nichols

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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-4,5bisphosphate (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 subsequent spontaneous wetting of the pore through the HBC gate region allowed K+ ion movement across the HBC and conduction through the channel. Further simulations reveal atomistic details of the opening process and highlight the role of pore-lining acidic residues in K+ conduction through Kir2 channels.

Original languageEnglish
JournalJournal of General Physiology
Volume152
Issue number1
DOIs
StatePublished - Jan 6 2020

Fingerprint Dive into the research topics of 'Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels'. Together they form a unique fingerprint.

Cite this