Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator

Myles H. Akabas, Christine Kaufmann, Tiffani A. Cook, Patrick Archdeacon

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

The cystic fibrosis transmembrane conductance regulator forms a chloride channel that is regulated by phosphorylation and intracellular ATP levels. The structure of the channel-forming domains is undetermined. To identify the residues lining this channel we substituted cysteine, one at a time, for 9 consecutive residues (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants were expressed in Xenopus oocytes. We determined the accessibility of the engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents added extracellularly. We assume that, among residues in membrane-spanning segments, only those lining the channel will be accessible to react with these hydrophilic reagents and that such a reaction would irreversibly alter conduction through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln-98 were accessible to the reagents. We conclude that these residues are in the channel lining. The periodicity of these residues is consistent with an α-helical secondary structure.

Original languageEnglish (US)
Pages (from-to)14865-14868
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number21
StatePublished - May 27 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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