Figure 11.

S4S5 and S6 domains and amino acids involved in electromechanical coupling in Kv4.2 and Shaker channels. (A) The previously studied S4S5_N, S4S5_C, and S6 domains in human Kv4.2 (16) are aligned with the corresponding Shaker domains (Shaker α₁ (orange) and Shaker α₂ (gray) represent two neighboring α-subunits). The numbered Kv4.2 residues in S4S5 (green) and S6 (blue) were tested for intra- and/or intersubunit interactions in this study. In Shaker, the S4S5_N residues I384 and T388 are thought to insert into a hydrophobic pocket formed by the S6 residues F481, Y483, and F484 of the same α-subunit (22). The S4S5_C residues R394, E395, and L398 of Shaker α₁, and the S6 residue Y485 of Shaker α₂ are involved in the RELY intersubunit interaction under the control of V476 (23). (B) S4S5 and S6 of two neighboring α-subunits in the Kv1.2-2.1 chimera crystal structure (19) illustrate putative intra- and intersubunit interactions in the Shaker channel. Domains involved in intrasubunit interactions between S4S5_N and S6 in Shaker α₁ are shown in red. The S6 domain of Shaker α₂ is nestled between S4S5_N of Shaker α₂ (intrasubunit interaction) and S4S5_C of Shaker α₁ (intersubunit interaction, magenta). Amino acid sequences and color coding correspond to (A). (C–F) Homology modeling of the Kv4.2 S4S5 (green) and S6 (blue) residues tested for intra- and/or intersubunit interactions in this study. The relevant portions of two neighboring α-subunits are shown, and the ribbon representation is colored according to (B). Kv4.2 coupling pairs: G309/I412 (C), S322/V404 (D), E323/V404 (E), and F326/V404 (F). The Kv4.2 residues are modeled on both α-subunits. They are shown in space-filling representation and the color coding corresponds to (A).