The pore of the KcsA channel, including the entire cavity up to the selectivity filter, participates in selectivity, rectification, and ion transport.

Abstract

Quantum calculations on the pore of the KcsA channel from gate to selectivity filter (SF) show how the motion of the K+ ions requires a coordination through states as a contact ion pair (CIP) just beyond the gate, then a solvent separated ion pair (SSIP) in the cavity, then again a CIP, as the ion approaches the selectivity filter (SF). Also, results on the hydration/resolvation by protein of the ion at the SF suggest a mechanism for rectification that depends on the water hydrogen bonded to the conserved threonines. K+ loses hydration water, switching to protein solvation at the SF; Na+ cannot move forward to the SF because of inability to lose hydration water to protein, so is selected out. Water confined in the cavity loses translational and rotational degrees of freedom, altering the competition between ion and protein for hydrating water. Calculations (seven positions, single ion, four positions, ion pairs) show limited barriers for a cluster with a pair of K+ ions, but large barriers for a single ion; it does not form exactly a similar SSIP at the entrance to the selectivity filter, but a SSIP at the cavity center and at the selectivity filter. Charge transfer as the ion moves through the pore can change the charge on the ion up to 0.03 q. Rectification occurs at the entrance to the SF, where the conserved threonine hydroxyls plus methyls interact with the ion near the first SF position, forming an effective ratchet and pawl that effects rectification, preventing an ion in the lowest SF position from reclaiming water in the cavity. Water–protein competition is a recurring theme as the ion moves through the pore.