A STRUCTURAL MOTIF FOR THE VOLTAGE-GATED POTASSIUM CHANNEL PORE

Mutation studies have identified a region of the S5-S6 loop of voltage -gated K+ channels (P region) responsible for tetraethylammonium (TEA) block and permeation/selectivity properties. We previously modeled a similar region of the Na+ channel as four beta-hairpins with the C str ands from each of the domains forming the external vestibule and with charged residues at the beta-turns forming the selectivity filter, How ever, the K+ channel P region amino acid composition is much more hydr ophobic in this area. Here we propose a structural motif for the K+ ch annel pore based on the following postulates (Kv2.1 numbering). (i) Th e external TEA binding site is formed by four Tyr-380 residues; P loop residues participating in the internal TEA binding site are four Met- 371 and Thr-372 residues. (ii) P regions form extended hairpins with b eta-turns in sequence ITMT. (iii) Only C ends of hairpins form the inn er walls of the pore. (iv) They are extended nonregular strands with b ackbone carbonyl oxygens of segment VGYGD facing the pore with the con formation BRLRL. (v) Juxtaposition of P loops of the four subunits for ms the pore. Fitting the external and internal TEA sites to TEA molecu les predicts an hourglass-like pore with the narrowest point (GYG) as wide as 5.5 Angstrom, suggesting that selectivity may be achieved by i nteractions of carbonyls with partially hydrated K+. Other potential c ation binding sites also exist in the pore.