title: Stoichiometry and novel gating mechanism within the cystic fibrosis transmembrane conductance regulator channel.
abstract: Despite its fundamental importance to the molecular mechanism underlying cystic fibrosis, many details of the structural basis for the cystic fibrosis transmembrane conductance regulator (CFTR) remain unknown. In addition, the possible interactions among the CFTR proteins have not been clearly demonstrated. In order to identify whether the CFTR channel pore is formed as a monomer or a multimer, we analysed the single-channel properties in patches of cell membrane that coexpressed selected CFTR mutants having significantly different single-channel properties. No hybrid channel opening patterns were observed. We therefore propose that the CFTR channel pore is indeed composed of a monomer. However, we also observed that coexisting CFTR monomers in the cell membrane facilitated the activation of individual CFTR channels. The functional upregulation of this CFTR channel opening probability and the different gating behaviour suggest dynamic conformational changes among the interacting CFTR proteins within the multimeric CFTR complex. Our findings regarding the CFTR monomer channel pore and the novel synergistic gating behaviour within the CFTR channel complex will help to resolve the remaining contradictions among previous studies regarding whether CFTR is a monomer or a multimer.
authors.affiliation: Department of Medical Function, School of Medicine, Yangtze University, Jingzhou, Hubei Province, 434023, China 49605795@qq.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Biology, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, Zhejiang Province, 321004, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Function, School of Medicine, Yangtze University, Jingzhou, Hubei Province, 434023, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Medical Function, School of Medicine, Yangtze University, Jingzhou, Hubei Province, 434023, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D003412:Cricetulus; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator