Xenbase Image ID: 128395

Figure 5. Cysteine accessibility is consistent with an S4 movement in which all three S4 charges significantly contribute to the effective gating charge. (A and B) Proposed S4 movement and charge–charge interactions in WT Hv channels according to present and previous (Gonzalez et al., 2010) cysteine accessibility data mapped onto the voltage-sensing domains from the Kv1.2-2.1 chimera channel structure (Long et al., 2007; A) and a closed-state model of Shaker K channels (Pathak et al., 2007; B). Positively charged S4 residues (R1, R2, and R3) and negatively charged glutamate residues (E1 and E2) are shown as ball and stick (except R2 = R258, which is space filled and colored yellow). Purple residues are only accessible from the extracellular solution in open channels and blue residues from the intracellular solution in closed channels (Gonzalez et al., 2010). Red residues (256 and 259) are not internally or externally accessible in closed or open channels (Gonzalez et al., 2010). Solid lines indicate proposed lipid bilayer boundaries, and dashed lines indicate proposed MTS accessibility as the result of water-filled crevices. Proposed positions of the charges of the three S4 arginine residues relative to the inaccessible portion of S4 are indicated. Assuming that the electrical field falls linearly over the inaccessible portion of S4, R255, R258, and R261 would contribute 0.80 e0, 1.0 e0, and 0.80 e0, respectively, to a total gating charge Q = 2.6 e0. This is similar to the contributions associated with these charges in FEP/MD simulations on the Kv1.2 voltage-sensing domain (Khalili-Araghi et al., 2010). (C and D) Two side views of the S1–S4 of an Hv1 channel monomer in the open (C) and closed (D) state rotated 180 degrees relative each other are shown in space fill. (E) Top view of the open state shown in C. (F) View from intracellular solution of the closed state shown in D. R258 is shown in yellow, and residues 256 and 259 are shown in red. R258 is accessible from the extracellular surface through a water-filled crevice (C and E) and from the intracellular surface through a water-filled crevice (D and F). Neither residue 256 nor 259 is visible from either side of the membrane in either closed or open states, consistent with earlier accessibility experiments (Gonzalez et al., 2010). Arrows show aqueous access to R258. Image published in: Gonzalez C et al. (2013) © 2013 Gonzalez et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license Larger Image Printer Friendly View

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