title: Grafting voltage and pharmacological sensitivity in potassium channels.
abstract: A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Fan
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Fuyun
authors.initials: F
authors.lastname: Tian
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.|University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
authors.forename: Zhaobing
authors.initials: Z
authors.lastname: Gao
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D000072417:Protein Domains
chemical_list: C498655:KCNK9 protein, human; D049990:Membrane Transport Modulators; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain