Voltage-sensor movements in the Eag Kv channel under an applied electric field

Area of Science:

• Biophysics
• Molecular Biology
• Structural Biology

Background:

• Voltage-dependent ion channels are crucial for cellular electrical activity, controlling ion flow across membranes.
• Their gating mechanism relies on the voltage-induced movement of charged residues, typically within S4 helices of voltage-sensor domains.
• Understanding these dynamics is key to comprehending cellular electrophysiology.

Purpose of the Study:

• To elucidate the structural basis of voltage-dependent gating in mammalian Eag potassium channels.
• To visualize the transmembrane displacement of the S4 helix in response to membrane potential changes.
• To investigate the interaction between K_v channels and the lipid bilayer environment.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to determine high-resolution structures.
• Structures were obtained from Eag channels reconstituted in lipid membrane vesicles subjected to an applied electric field.
• Multiple conformational states were captured to map S4 helix movement.

Main Results:

• The S4 helix was observed to move two helical turns towards the cytoplasm upon hyperpolarization.
• This 'down' conformation positions the S4 helix as an extended interfacial helix, incompatible with an open pore.
• Detailed interactions of charged residues with the membrane and channel-induced membrane reshaping were visualized.

Conclusions:

• The observed S4 helix movement directly explains how hyperpolarizing voltages lock the Eag K_v channel pore in a closed state.
• These findings provide a structural mechanism for voltage sensing and gating in this class of potassium channels.
• The study highlights the significant interplay between ion channels and their native lipid membrane environment.