title: Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.
abstract: Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.
authors.affiliation: Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Éva
authors.initials: É
authors.lastname: Lörinczi
authors.affiliation: Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Gómez-Posada
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: de la Peña
authors.affiliation: Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Tomczak
authors.affiliation: Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Fernández-Trillo
authors.affiliation: Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Leipscher
authors.affiliation: Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.|Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, 37073 Göttingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Stühmer
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros
authors.affiliation: Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Luis A
authors.identifier: http://orcid.org/0000-0003-1375-4349
authors.initials: LA
authors.lastname: Pardo
mesh_terms: D000818:Animals; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D024642:Potassium Channels, Voltage-Gated
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