Conserved gating hinge in ligand- and voltage-dependent K+ channels

Area of Science:

• Molecular Biology
• Biophysics
• Structural Biology

Background:

• Ion channels regulate cellular transport.
• Gating, the process of opening and closing ion channels, is crucial for cellular function.
• Previous studies proposed a glycine hinge mechanism for gating in voltage-independent potassium (K+) channels.

Purpose of the Study:

• To investigate if a similar glycine hinge conformational change underlies pore opening in eukaryotic voltage-dependent potassium (K+) channels.
• To examine the role of the gating hinge in Shaker and BK channels.

Main Methods:

• Site-directed mutagenesis of the gating hinge glycine residues in Shaker and BK channels.
• Assessment of channel pore opening and gating properties following mutations.

Main Results:

• Mutations of the gating hinge glycine in Shaker channels prevented pore opening, which was restored by introducing a secondary glycine.
• A proline mutation at the gating hinge of Shaker channels favored the open state.
• Mutations to alanine in BK channels significantly hindered opening in a graded manner.
• These findings indicate a conserved gating mechanism across different types of K+ channels.

Conclusions:

• The inner helix bending at a conserved glycine gating hinge is essential for the pore opening of both voltage-dependent and independent potassium channels.
• This study supports a universal gating mechanism for potassium channels, involving a conserved glycine hinge.
• The findings have implications for understanding ion channel function and developing targeted therapeutics.