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Stoichiometry and novel gating mechanism within the cystic fibrosis transmembrane conductance regulator channel
Author(s) -
Qian Feng,
Li Tao,
Yang Fei,
Liu Lian
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2014.081034
Subject(s) - cystic fibrosis transmembrane conductance regulator , gating , cystic fibrosis , chemistry , conductance , biophysics , transmembrane protein , microbiology and biotechnology , downregulation and upregulation , regulator , membrane , monomer , biochemistry , biology , genetics , physics , receptor , gene , condensed matter physics , organic chemistry , polymer
New FindingsWhat is the central question of this study? We aimed to demonstrate the possibility that the cystic fibrosis transmembrane conductance regulator (CFTR) forms higher‐order multimers during channel pore formation and/or channel gating using functional evidence.What is the main finding and its importance? The majority of our electrophysiological data suggested that the CFTR channel pore is formed by transmembrane domains of only one CFTR molecule as a monomer. However, we also observed functional upregulation of CFTR activation in patches, which implies interprotein interactions among CFTR molecules. Our findings will help to resolve many contradictions among previous reports regarding whether CFTR is a monomer or a multimer.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.