Structure basis of CFTR folding, function and pharmacology

Tzyh Chang Hwang, Ineke Braakman, Peter van der Sluijs, Isabelle Callebaut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The root cause of cystic fibrosis (CF), the most common life-shortening genetic disease in the Caucasian population, is the loss of function of the CFTR protein, which serves as a phosphorylation-activated, ATP-gated anion channel in numerous epithelia-lining tissues. In the past decade, high-throughput drug screening has made a significant stride in developing highly effective CFTR modulators for the treatment of CF. Meanwhile, structural-biology studies have succeeded in solving the high-resolution three-dimensional (3D) structure of CFTR in different conformations. Here, we provide a brief overview of some striking features of CFTR folding, function and pharmacology, in light of its specific structural features within the ABC-transporter superfamily. A particular focus is given to CFTR's first nucleotide-binding domain (NBD1), because folding of NBD1 constitutes a bottleneck in the CFTR protein biogenesis pathway, and ATP binding to this domain plays a unique role in the functional stability of CFTR. Unraveling the molecular basis of CFTR folding, function, and pharmacology would inspire the development of next-generation mutation-specific CFTR modulators.

Original languageEnglish
JournalJournal of Cystic Fibrosis
StateAccepted/In press - 2022


  • ABC transporter
  • CFTR
  • corrector
  • modulator
  • potentiator


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