In Science, MacKinnon and colleagues now present two papers on the structure of a mammalian voltage-dependent K+ (Kv) channel, Kv1.2, of the Shaker family. Kv channels conduct K+ ions across membranes in response to changes in membrane voltage. Previous structural information on K+ channels has come from studies on prokaryotic channels, because they can be easily expressed at high levels. However, these new papers describe the 2.9-Å-resolution crystal structure of the rat brain Kv1.2 channel in complex with its β2 subunit (β subunits can regulate mammalian Kv channels in vivo).
The tetrameric complex, which has fourfold symmetry, is composed of a transmembrane region that contains the pore and the four voltage sensors, an intracellular (T1) domain that is formed by the N termini of the four Kv1.2 subunits, and four β2 subunits that are bound to the T1 domain. The pore, which seems to be open, is similar to those of prokaryotic K+ channels, although the curvature of the inner helices of the Kv1.2 channel is the result of a conserved Pro-X-Pro sequence rather than a Gly residue. The pore is linked to the cytoplasm by large side portals that are located between the pore and T1 domain. The location and properties of the N termini of the T1 domain and β subunits and the electrostatic properties of the portals indicate that these termini might function as inactivation peptides that plug the portals. The structure has also indicated how β subunits might regulate channel function in other ways. Finally, as the voltage sensors seem to be in their native conformation, it has provided a simple view of how membrane voltage affects the probability of the channel being open. REFERENCESLong, S. B. et al. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 7 July 2005 (10.1126/science.1116269)Long, S. B. et al. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 7 July 2005 (10.1126/science.1116270)
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