title: Role of intracellular domains in the function of the herg potassium channel.
abstract: The functional role of the large intracellular regions (which include the cyclic nucleotide binding domain, cNBD, and the Per-Arnt-Sim domain, PAS) in the herg channel is not well understood. We have studied possible interactions of the cNBD with other parts of the channel protein using lysine mutations to disrupt such interactions. Some lysine mutations caused significant right shifts in the voltage dependence of inactivation; almost all the mutants caused speeding up of deactivation time course. In a homology model of the cNBD, lysine mutations that affected both inactivation and deactivation lie in a hydrophobic band on the surface of the structure of this domain. Some known mutations in the Long QT Syndrome type 2, with effects on deactivation, are located at residues close to hydrophobic bands on the cNBD and the PAS domains. Such bands of residues in these intracellular domains may play an important part in channel function.
authors.affiliation: Faculty of Biological Sciences, University of Leeds, Leeds, UK.
authors.forename: Moza
authors.initials: M
authors.lastname: Al-Owais
authors.forename: Kate
authors.initials: K
authors.lastname: Bracey
authors.forename: Dennis
authors.initials: D
authors.lastname: Wray
mesh_terms: D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008133:Long QT Syndrome / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D009712:Nucleotides, Cyclic / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D009712:Nucleotides, Cyclic