title: Hydrophobic substitution mutations in the S4 sequence alter voltage-dependent gating in Shaker K+ channels.
abstract: Voltage-activated Na+, Ca2+, and K+ channels contain a common motif, the S4 sequence, characterized by a basic residue at every third position interspersed mainly with hydrophobic residues. The S4 sequence is proposed to function as the voltage sensor and to move in response to membrane depolarization, triggering conformational changes that open the channel. This hypothesis has been tested in previous studies which revealed that mutations of the S4 basic residues often shift the curve of voltage dependence of activation along the voltage axis. We find that comparable or larger shifts are caused by conservative substitutions of hydrophobic residues in the S4 sequence of the Shaker K+ channel. We suggest that the S4 structure plays an essential role in determining the relative stabilities of the closed and open states of the channel.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
authors.forename: G A
authors.initials: GA
authors.lastname: Lopez
authors.forename: Y N
authors.initials: YN
authors.lastname: Jan
authors.forename: L Y
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004553:Electric Conductivity / Q000502:physiology*; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009865:Oocytes / Q000502:physiology / Q000648:ultrastructure; D015221:Potassium Channels / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D008565:Membrane Proteins; D015221:Potassium Channels