Tuning of CFTR chloride channel function by location of positive charges within the pore

Résultat de recherche: Articleexamen par les pairs

24 Citations (Scopus)

Résumé

High unitary Cl- conductance in the cystic fibrosis transmembrane conductance regulator Cl- channel requires a functionally unique, positively charged lysine residue (K95) in the inner vestibule of the channel pore. Here we used a mutagenic approach to investigate the ability of other sites in the pore to host this important positive charge. The loss of conductance observed in the K95Q mutation was >50% rescued by substituting a lysine for each of five different pore-lining amino acids, suggesting that the exact location of the fixed positive charge is not crucial to support high conductance. Moving the positive charge also restored open-channel blocker interactions that are lost in K95Q. Introducing a second positive charge in addition to that at K95 did not increase conductance at any site, but did result in a striking increase in the strength of block by divalent Pt(NO2)42- ions. Based on the site dependence of these effects, we propose that although the exact location of the positive charge is not crucial for normal pore properties, transplanting this charge to other sites results in a diminution of its effectiveness that appears to depend on its location along the axis of the pore.

Langue d'origineEnglish
Pages (de-à)1719-1726
Nombre de pages8
JournalBiophysical Journal
Volume103
Numéro de publication8
DOI
Statut de publicationPublished - oct. 17 2012

Note bibliographique

Funding Information:
This work was supported by the Canadian Institutes of Health Research. Y.E.H. is a Cystic Fibrosis Canada Postdoctoral Fellow.

ASJC Scopus Subject Areas

  • Biophysics

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Empreinte numérique

Plonger dans les sujets de recherche 'Tuning of CFTR chloride channel function by location of positive charges within the pore'. Ensemble, ils forment une empreinte numérique unique.

Citer

El Hiani, Y., & Linsdell, P. (2012). Tuning of CFTR chloride channel function by location of positive charges within the pore. Biophysical Journal, 103(8), 1719-1726. https://doi.org/10.1016/j.bpj.2012.09.020