Understanding nucleotide binding and CFTR ion channel gating: how many cycles?

Abstract

Evaluation of: Tsai MF, Li M, Hwang TC. Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel. J. Gen. Physiol. 135(5), 399–414 (2010).

The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP binding cassette transporter forming a chloride (Cl^-) channel whose opening/closing (a mechanism named gating) depends on a complex regulation by the phosphorylation/dephosphorylation of the regulatory R-domain and ATP binding/hydrolysis occurring on nucleotide-binding domains. Understanding how the channel is gated by ATP is important, since many mutations in the CFTR gene causing cystic fibrosis are located in these nucleotide-binding domains, and the exact molecular mechanism linking the ATPase cycle to Cl^- permeation remains unclear and controversial. In their recent paper, Tsai et al. examined the ATP gating of CFTR in great detail, highlighting new, exciting and provocative concepts.

Keywords::

• ABC transporters
• ATP gating
• CFTR
• chloride channels
• cystic fibrosis
• NBD
• nucleotide binding

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.