Control of KirBac3.1 potassium channel gating at the interface between cytoplasmic domains.

KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures of KirBac3.1 have provided important insights into the structural basis of gating in Kir channels. In this study, we demonstrate that KirBac3.

Simulation-based prediction of phosphatidylinositol 4,5-bisphosphate binding to an ion channel.

Protein-lipid interactions regulate many membrane protein functions. Using a multiscale approach that combines coarse-grained and atomistic molecular dynamics simulations, we have predicted the binding site for the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) on the Kir2.2 inwardly rectifying (Kir) potassium channel.

State-independent intracellular access of quaternary ammonium blockers to the pore of TREK-1.

We previously reported that TREK-1 gating by internal pH and pressure occurs close to or within the selectivity filter. These conclusions were based upon kinetic measurements of high-affinity block by quaternary ammonium (QA) ions that appeared to exhibit state-independent accessibility to their binding site within the pore. Intriguingly, recent crystal structures of two related K2P potassium channels were also both found to be open at the helix bundle crossing.

Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating.

KirBac channels are prokaryotic homologs of mammalian inwardly rectifying (Kir) potassium channels, and recent crystal structures of both Kir and KirBac channels have provided major insight into their unique structural architecture. However, all of the available structures are closed at the helix bundle crossing, and therefore the structural mechanisms that control opening of their primary activation gate remain unknown. In this study, we engineered the inner pore-lining helix (TM2) of KirBac3.