An Ingenious Filter: the Structural Basis for Ion Channel Selectivity

Abstract

channel from Streptomyces lividans, was readily overex-pressed in bacteria (Schrempf et al., 1995). Its primary sequence is related to the class of ion-selective channels called inwardly rectifying channels, as evidenced by the presence of two putative transmembrane helices with the ion selectivity–determining P region residing Neurobiology has taken a giant step forward: we know, between them (see Figure 1, inset). The amino acid se-for the first time, the crystal structure of an ion channel. quence closely resembles a portion of that of voltage-MacKinnon and collaborators (Doyle et al., 1998) have dependent, six transmembrane K ϩ channels, though won a two year long race with perhaps a dozen other these channels are not voltage dependent. Because of laboratories around the world to determine with 3.2 A ˚ KcsA's topological kinship to eukaryotic K ϩ channels, resolution the structure of a bacterial potassium chan-many investigators immediately surmised that KcsA nel, known as KcsA. This achievement is a milestone in would be the most viable option, at least for the time our understanding of the basis for the electrical excit-being, for elucidating the three-dimensional structure of ability of cells and also marks the start of a new era of an ion-selective channel. The newly discovered structure of KcsA is testament to that vision. channel biophysics, in which we will be finally able to Structure of the KcsA Protomer relate ion channel function to the arrangement of atoms The structure reported by MacKinnon and colleagues in channel proteins. We can now see that the potassium confirms sequence predictions that each subunit folds channel selectivity filter, the region of the protein re-into two antiparallel transmembrane helices (M1 and sponsible for permitting the passage of potassium ions M2) interrupted by the P region. The P region consists and excluding sodium ions, is a 12-A ˚-long, 3-A ˚-wide of a short " pore helix " followed by a " loop region " consti-pore with walls constructed from main chain oxygen tuting the major selectivity filter (see Figure 1). The core atoms. of the selectivity filter consists of five well-conserved The Overall Structure signature amino acids: TVGYG. The four subunits are All voltage-dependent, ion-selective channels share the packed around a pore at the center of the tetramer architectural " plan of four. " Na ϩ-and Ca 2ϩ-selective through interactions between the " inner helices " (M2), channels consist of a single polypeptide chain con-the short pore helices, and …

DOI: 10.1016/S0896-6273(00)80462-6

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Cite this paper

@article{Choe1998AnIF, title={An Ingenious Filter: the Structural Basis for Ion Channel Selectivity}, author={Senyon Choe and Robert G . Robinson}, journal={Neuron}, year={1998}, volume={20}, pages={821-823} }