An SS1-SS2 beta-barrel structure for the voltage-activated potassium channel

Area of Science:

• Biophysics
• Structural Biology
• Molecular Biology

Background:

• Voltage-gated potassium channels are crucial for cellular electrical activity.
• The precise structure of the pore-lining region is key to channel function and selectivity.
• Previous models often focused on alpha-helical structures.

Purpose of the Study:

• To investigate the feasibility of a beta-barrel structure for the pore-lining region of voltage-gated potassium channels.
• To develop and evaluate computational models of potential beta-barrel structures.
• To compare model predictions with experimental data, specifically tetraethylammonium (TEA) block.

Main Methods:

• Characterization of 12 antiparallel beta-barrel models.
• Analysis of beta-strand arrangement, hairpin turns, and strand orientation (clockwise/counterclockwise).
• Evaluation of models based on potential energy predictions and experimental TEA block data.

Main Results:

• All models featured inward-projecting aromatic side-chains potentially regulating channel selectivity.
• Models with an odd number of amino acids in the hairpin turn predicted specific residue orientations.
• Two models showed consistency with external TEA block data; one model (T439 CCW 3:5) best fit both external and internal TEA block data.

Conclusions:

• A beta-barrel structure is a feasible model for the pore-lining region of voltage-gated potassium channels.
• Specific structural features, like hairpin turn composition and strand orientation, influence model validity.
• The T439 CCW 3:5 model provides a strong candidate structure consistent with biophysical channel block data.