An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding

G. Yellen, D. Sodickson, Tsung-Yu Chen, M. E. Jurman

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-Δ K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a K(d) for Cd2+ of ~0.2 μM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein.

Original languageEnglish (US)
Pages (from-to)1068-1075
Number of pages8
JournalBiophysical Journal
Volume66
Issue number4
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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