Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain

Figure 5. The tilt-shift model. (a) Evaluation of the distance changes, from up state to down state, derived from different gating models in the KvAP VSD. Left, ribbon representation of the up-state VSD model (gray) after MD equilibration and overlapped with putative models based on the helix-screw (magenta), paddle (orange) and tilt-shift (blue) gating mechanisms. Right, expected distance changes against experimental distance differences for the three down states. Gray region indicates the uncertainty of measurement. (b) An alternative explanation for the existing KvAP biotin-streptavidin trapping experiments. All the established state-dependent accessibilities on KvAP focused on the region of 121–125 (in yellow). The paddle model predicts a 15-Å to 20-Å downward S4 movement to account for the streptavidin trapping data (accessibility from the bottom is indicated). (c) ΔΠNiEdda mapped on to the crystal structure, showing water penetration deep into the bottom crevice, where the region 121–125 is only ∼5 Å above the uppermost NiEdda penetration. (d) Cartoon representation of the tilt-shift model on KvAP VSD. The ∼25° tilt and ∼2-Å downward shift of S4 could generate a movement of ∼3–4 Å of the S4-S5 linker, sufficient to open the pore.