Structure and Packing Orientation of Transmembrane Segments in Voltage-Dependent Channels: Lessons from Perturbation Analysis

The past 2 yr have been extraordinary in terms of advances in our understanding of how ion channels work. Nowhere has this dizzying progress been more evident than in the study of the voltage-dependent K⁺ channel family, K_v. The great catalyst has been, of course, the high-resolution structure of the Streptomyces lividans K⁺ channel KcsA (Doyle et al. 1998), a breakthrough that brought into sharp focus more than three decades of electrophysiological studies on K⁺ channels. The structure of KcsA shows a remarkably efficient blueprint for ion permeation: a short selectivity filter, where carbonyl oxygens are likely to interact with dehydrated ions, followed by an energetically favorable water-filled cavity, capped at the intracellular end by a closely packed bundle of helices restricting ion flow in the closed state. Gating mechanisms, however, are...