FIGURE 8.

Structure of the pore and selectivity filter of NavAb and CavAb. A, architecture of the NavAb pore. Purple, Glu¹⁷⁷ side chains; gray, pore volume. The S5 and S6 segments and the P loop from two lateral subunits are shown (53). B, top view of the ion selectivity filter. Symmetry-related molecules are colored white and yellow; P-helix residues are colored green. Hydrogen bonds between Thr¹⁷⁵ and Trp¹⁷⁹ are indicated by gray dashes. Electron densities from F_o − F_c omit maps are contoured at 4.0 σ (blue and gray), and subtle differences can be appreciated (small arrows) (53). C, side view of the ion selectivity filter. Glu¹⁷⁷ (purple) interactions with Gln¹⁷², Ser¹⁷⁸, and the backbone of Ser¹⁸⁰ are shown in the far subunit. F_o − F_c omit map at 4.75 σ (blue) and putative cations or water molecules (red spheres, Ion_EX) are shown. Electron density around Leu¹⁷⁶ (gray; F_o − F_c omit map at 1.75 σ) and a putative water molecule are shown (gray sphere). Na⁺ coordination sites: Site_HFS, Site_CEN, and Site_IN (53). D, CavAb selectivity filter. Electron density at the selectivity filter of ¹⁷⁵TLDDWSN¹⁸¹ is shown. The 2F_o − F_c electron density map (contoured at 2 σ) of select residues in the selectivity filter with two diagonally opposed subunits is shown in stick format, the Ca²⁺ ions along the ion pathway are shown in green spheres, and water molecules are shown in red spheres. Note that it is likely that adjacent calcium-binding sites are not occupied simultaneously because of electrostatic repulsion. Our model is that the site at Asp¹⁸¹ in the outer vestibule and the high-field-strength site at Asp¹⁷⁷ are occupied together, the sites at Asp¹⁷⁸ and the carbonyl sites at Leu¹⁷⁶/Thr¹⁷⁵ are occupied together, and the selectivity filter and vestibule oscillate between these two ion occupancies to mediate rapid conductance.