Figure 5. Structural changes resulting from rearrangements in the selectivity filter region.
(a) Representation of the channel structures in the closed (left) and open (right) states. For clarity, only S6 (white) and pore helix (red) are shown for three subunits. The side chains of Y671 (at the upper gate) and I679, I675 (bottom gate) are highlighted using a stick representation and the permeant Na+ ions are shown as purple spheres. Blue shades show the average density of water molecules calculated along the MD trajectory. Note how the water density forms a continuum throughout the pore only when in the open state. (b) Proposed mechanism for the opening and closing of the upper gate: the rearrangement of the four planar groups of residue 671 from the ‘vertical’ to the ‘horizontal ring’ configuration is accompanied by a change in the tilt (with respect to the membrane plane) of the N-terminus section of S6 and of the pore-helix. In particular, the motion of the pore-helix regulates the effective pore radius at the level of the selectivity filter. The outward motion of both the pore helix and the aromatic at position 671 cause a reduction in water and ion accessibility. (c) Molecular structure sampled along the MD trajectory of the coumarin mutant in the closed and open states. For clarity, only S6 and the pore helix are shown with two of the four subunits rendered as gray shading. The coumarin moieties are highlighted using a space-filling representation. Left: closed state. The hydroxyl group of coumarin is able to establish the same H-bonding interactions with the carbonyl group of the pore-helix observed in the wild type. Right: open state. A permeant Na+ ion (yellow sphere) is shown together with its first solvation shell (sticks). Note how the hydroxyl groups from coumarin contribute to the shell of neighbors of the ion.
Figure 5—figure supplement 1. Additional views of the coumarin mutant structures.
