Localization the PUFA action site. (A) Extracellular view of the Shaker K channel in an open state (based on the Kv1.2/2.1 chimera; Long et al., 2007). Only one VSD and part of the pore domain are shown. The blue residues are the four most extracellular gating charges (R362, R365, R368, and R371). The selectivity filter is shown in cyan. Green residues (I325, A359, and I360) have the largest impact on the PUFA-induced shift of the G-V curve, the yellow residue (T329) has a smaller but significant effect on the PUFA-induced shift, and red residues have no significant effects on the PUFA-induced shifts. The negative charge denotes an approximate position of the PUFA carboxyl charge affecting the voltage sensitivity of the Shaker K channel. (B) Side view of the channel with I325, A359, and I360 in green, T329 in yellow, and residues with no significant effects on the PUFA-induced shifts in red. Not investigated residues in S3 are shown in cyan, and those in S4 are shown in blue. All residues in space fill.