Elongation of Outer Transmembrane Domain Alters Function of Miniature K+ Channel Kcv
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The virus-coded channel Kcv has the typical structure of a two-transmembrane domain K+ channel. Exceptional are its cytoplasmic domains: the C terminus basically ends inside the membrane and, hence, precludes the formation of a cytoplasmic gate by the so-called bundle crossing; the cytoplasmic N terminus is composed of only 12 amino acids. According to structural predictions, it is positioned in the membrane/aqueous interface and connected via a proline kink to the outer transmembrane domain (TM1). Here, we show that this proline kink affects channel function by determining the position of TM1 in the membrane bilayer. Extension of the hydrophobic length of TM1 by either eliminating the proline kink or introducing an alanine in TM1 augments a time- and voltage-dependent inward rectification of the channel. This suggests that the positional information of TM1 in the bilayer is transmitted to a channel gate, which is not identical with the cytoplasmic bundle crossing.
KeywordsK+ channel gating Transmembrane domain Viral channel Kcv Ion selectivity Hydrophobic mismatch
We are grateful to Rikard Blunck (Los Angeles) and Antoinette Killian (Utrecht) for helpful discussions. We also thank Jack Dainty (Norwich) for help with the manuscript. Particular thanks to Gisela Marx for excellent technical assistance. This work was supported in part by the Deutsche Forschungsgemeinschaft (to G. T. and S. M. K.); Fonds der Chemischen Industrie and the Adolf-Messer-Stiftung (to S. M. K.); the Ministero Istruzione Università e Ricerca, Progetto Fondo per gli Investimenti della Ricerca di Base (to A. M.); National Institutes of Health grant GM32441 (to J. V. E.); and grant P20RR15635 from the COBRE Program of the National Center for Research Resources (to J. V. E.).
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