title: alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.
abstract: Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain.
authors.affiliation: Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li-Smerin
authors.forename: D H
authors.initials: DH
authors.lastname: Hackos
authors.forename: K J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D010507:Periodicity; D017354:Point Mutation / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated