FIGURE 3.

Models of NaChBac VSDs with S4 in innermost and transition positions. Coloring, orientation, and labels are the same as in Fig. 1. Closed models are numbered according to the number of S4 arginine guanidium groups located above the transition barrier, as indicated by rectangles. Arrows indicate plausible pathways for activation at positive voltages (red), and deactivation at negative voltages (green), if voltage-dependent changes in secondary structure occur more rapidly than the transitions between the Closed₀ and Closed₁ and Closed₂ models. (A) A rigid helical screw mechanism, in which S4 maintains a predominately α-helical conformation as it transitions from hyperpolarized closed to Open₁ conformations. (B) An elastic helical screw mechanism, in which the N-terminus portion of S4 adopts a 3₁₀ helical secondary structure in closed conformations. The MlotiK crystal structure was used as a template for the S2, S3b, and S4 portions of Closed_2b and Closed_3b models. The primary difference between the Closed_2b and Closed_3b models is the conformation of the R3 side chain.