title: Voltage dependent activation of potassium channels is coupled to T1 domain structure.
abstract: The T1 domain, a highly conserved cytoplasmic portion at the N-terminus of the voltage-dependent K+ channel (Kv) alpha-subunit, is responsible for driving and regulating the tetramerization of the alpha-subunits. Here we report the identification of a set of mutations in the T1 domain that alter the gating properties of the Kv channel. Two mutants produce a leftward shift in the activation curve and slow the channel closing rate while a third mutation produces a rightward shift in the activation curve and speeds the channel closing rate. We have determined the crystal structures of T1 domains containing these mutations. Both of the leftward shifting mutants produce similar conformational changes in the putative membrane facing surface of the T1 domain. These results suggest that the structure of the T1 domain in this region is tightly coupled to the channel's gating states.
authors.affiliation: Division of Neuroscience, S613, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Cushman
authors.forename: M H
authors.initials: MH
authors.lastname: Nanao
authors.forename: A W
authors.initials: AW
authors.lastname: Jahng
authors.forename: D
authors.initials: D
authors.lastname: DeRubeis
authors.forename: S
authors.initials: S
authors.lastname: Choe
authors.forename: P J
authors.initials: PJ
authors.lastname: Pfaffinger
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001048:Aplysia / Q000737:chemistry*; D017124:Conserved Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D004553:Electric Conductivity; D015640:Ion Channel Gating; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051637:Shaker Superfamily of Potassium Channels; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels