Molecular dynamics simulations reveal how KCNE1 shifts the coupling mechanism between the activation state of the Voltage Sensor Domain of the KV7.1 channel and the conformation of its Pore Domain.
This computational study elucidates the molecular mechanism by which KCNE1 modulates the KV7.1 channel, which is responsible for the IKs repolarization current in cardiomyocytes.
Abstract The IK S current is diffused through the plasma membranes of cardiomyocytes during the last phase of the cardiac action potential. This repolarization current is conducted by a tetrameric protein complex derived from the co-expression of four voltage-gated potassium channel K V 7.1 α-subunits and KCNE1 ancillary subunits from KCNQ1 and KCNE1 genes, respectively. We studied here the conformational space of K V 7.1 in presence and absence of KCNE1, by building transmembrane models of their known Resting, Intermediate, and Activated states. We conducted Molecular Dynamics simulations of these models in lipid bilayers including the phosphatidyl-inositol-4,5-bisphosphate (PIP 2 ) lipids. The comparative analysis of MD trajectories obtained for the K V 7.1 and IK S models reveals how KCNE1 shifts the coupling mechanism between the activation state of the Voltage Sensor Domain of the channel and the conformation (open or closed) of its Pore Domain.
Kongmeneck et al. (Wed,) conducted a other in Cardiac action potential repolarization (IKs current). KCNE1 ancillary subunits vs. Absence of KCNE1 was evaluated on Coupling mechanism between the Voltage Sensor Domain and Pore Domain. Molecular dynamics simulations reveal how KCNE1 shifts the coupling mechanism between the activation state of the Voltage Sensor Domain of the KV7.1 channel and the conformation of its Pore Domain.
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