Decoupling Gating and Selectivity in the Mechanosensitive OSCA3.1 Channel: A Free Energy Landscape and Hydration...

Area of Science:

• Plant biology
• Biophysics
• Structural biology

Background:

• OSCA family proteins are crucial mechanosensitive ion channels in plants.
• They play a key role in sensing osmotic stress and drought adaptation.
• The dynamic gating, ion selectivity, and cooperative mechanisms of OSCA channels remain poorly understood.

Purpose of the Study:

• To investigate the conformational dynamics and ion permeation mechanisms of the Arabidopsis OSCA3.1 channel.
• To elucidate the gating process and the energetic basis for selective ion transport.

Main Methods:

• Molecular dynamics (MD) simulations, including conventional MD, steered MD (SMD), and umbrella sampling.
• Analysis of conformational changes, hydrophobic gate dismantling, and ion permeation free energy barriers.

Main Results:

• Channel opening involves significant conformational rearrangement, primarily M6 helix tilting, dismantling the hydrophobic gate.
• Both K+ and Ca2+ face substantial energy barriers for permeation, with Ca2+ facing a significantly higher barrier (~53 kcal/mol) than K+ (~30 kcal/mol).
• The pore's electrostatic potential facilitates cation passage, with a neutral hydrophobic region and an electronegative lower region.

Conclusions:

• OSCA3.1 gating is a cooperative process driven by helical motion.
• The channel exhibits "kinetic selectivity," favoring K+ over Ca2+ permeation due to energetic differences, not absolute blockage.
• This provides an atomistic mechanism for differential ion flux regulation during osmotic stress sensing in plants.