Molecular dynamics simulations revealed that two PIP2 lipids are necessary to stabilize each state of the IKs channel, with KCNE1 interacting with both binding sites to prevent pore opening.
Molecular dynamics simulations reveal that two PIP2 lipids per monomer are required to stabilize the IKS channel states, providing structural insights into how auxiliary KCNE subunits modulate ion channels.
Abstract The phosphatidyl-inositol-4,5-bisphosphate (PIP 2 ) lipid has been shown to be crucial for the coupling between the voltage sensor and the pore of the potassium voltage-gated K V 7 channel family, especially the K V 7.1 channel. The latter, expressed in the myocardium membrane is complexed with its auxiliary subunits, KCNE1 to generate the so-called IK S current. We present here molecular models of transmembrane domain of this complex in its three known states, namely the Resting/Closed (RC), the Intermediate/Closed (IC), and the Activated/Open (AO), robustness of which is assessed by agreement with a range of biophysical data. Molecular Dynamics (MD) simulations of these models embedded in a lipid bilayer including phosphatidyl-inositol-4,5-bisphosphate (PIP 2 ) lipids show that in presence of KCNE1, two PIP 2 lipids are necessary to stabilize each state. The simulations also show that KCNE1 interacts with both PIP 2 binding sites, forming a tourniquet around the pore and preventing its opening. The present investigation provides therefore key molecular elements that govern the role of PIP 2 in KCNE1 modulation of IK S channels, possibly a common mechanism by which auxiliary KCNE subunits might modulate a variety of other ion channels.
Kongmeneck et al. (Wed,) reported a other. Molecular Dynamics (MD) simulations was evaluated on Interaction between PIP2, KCNE1, and the KV7.1 channel pore. Molecular dynamics simulations revealed that two PIP2 lipids are necessary to stabilize each state of the IKs channel, with KCNE1 interacting with both binding sites to prevent pore opening.