@article{0aef8ae3015f443589d115ac073d482b,
title = "CFTR: Ligand exchange between a permeant anion ([Au(CN)2] -) and an engineered cysteine (T338C) blocks the pore",
abstract = "Previous attempts to identify residues that line the pore of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel have utilized cysteine-substituted channels in conjunction with impermeant, thiol-reactive reagents like MTSET+ and MTSES-. We report here that the permeant, pseudohalide anion [Au(CN)2]- can also react with a cysteine engineered into the pore of the CFTR channel. Exposure of Xenopus oocytes expressing the T338C CFTR channel to as little as 100 nM[Au(CN)2]- produced a profound reduction in conductance that was not reversed by washing but was reversed by exposing the oocytes to a competing thiol like DTT (dithiothreitol) and 2-ME (2-mercaptoethanol). In detached, inside out patches single-channel currents were abolished by [Au(CN)2]- and activity was not restored by washing [Au(CN)2]- from the bath. Both single-channel and macroscopic currents were restored, however, by exposing [Au(CN) 2]--blocked channels to excess [CN]-. The results are consistent with the hypothesis that [Au(CN)2]- can participate in a ligand exchange reaction with the cysteine thiolate at 338 such that the mixed-ligand complex, with a charge of -1, blocks the anion conduction pathway.",
author = "Serrano, \{Jos{\'e} R.\} and Xuehong Liu and Borg, \{Erik R.\} and Alexander, \{Christopher S.\} and Shaw, \{C. Frank\} and Dawson, \{David C.\}",
year = "2006",
doi = "10.1529/biophysj.105.078899",
language = "English (US)",
volume = "91",
pages = "1737--1748",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Elsevier Inc.",
number = "5",
}