ABSTRACT
In addition to being a model of pore properties, KcsA recently also served as a model for studying the structural dynamics that underly opening and closing of an ion channel. In KcsA, gating is triggered by changes in intracellular pH, with acidification and alkalinization leading to opening and closing (or activation and deactivation) of the channel, respectively [46,79]. Using site-directed spin labeling together with EPR spectroscopy, Perozo and his group showed which parts of the channel protein move during gating and which remain immobile [80]. Figure 7A presents the resulting mechanism of channel activation. In the closed state, the pore is occluded (or at least reduced to a diameter small enough to prevent passage of hydrated K+ ions) by the TM2 bundle (left panel in Fig. 7A). Driven by a yet unkown pH-dependent step, all four TM2s rotate counterclockwise (when viewed from the extracellular side) and swing away from the pore. Either simultaneously or driven by this movement, the TM1 helices also rotate in a counterclockwise direction, while parts of the P helix move toward or away from the symmetry axis of the pore [80,81]. Because of their numerous contacts with TM2, the rearrangements seen with TM1 and the P helix are expected to fill spaces left open by the TM2 movement. As a consequence of these rotation-translocation processes, the pore diameter at the crossing of the TM2 bundle is increased and thereby widened enough to allow for passage of hydrated K+ ions (right panel in Fig. 7A). As might have been anticipated, the residues of the selectivity filter remain largely immobile during these gating-related rearangements in the KcsA structure.
