Molecular Structure of the Human CFTR Ion Channel

Fangyu Liu, Zhe Zhang, L. Csanády, David C. Gadsby, Jue Chen

Research output: Contribution to journalArticle

158 Citations (Scopus)


The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening. By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphorylation of the R domain is enabled by its infrequent spontaneous disengagement, which also explains residual ATPase and gating activity of dephosphorylated CFTR. From comparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop transition in transmembrane helix 8, which likely forms the structural basis for CFTR's channel function.

Original languageEnglish
Pages (from-to)85-92
Number of pages8
Issue number1
Publication statusPublished - Mar 23 2017


  • ABC transporter
  • anion channel
  • cryo-EM
  • human CFTR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Liu, F., Zhang, Z., Csanády, L., Gadsby, D. C., & Chen, J. (2017). Molecular Structure of the Human CFTR Ion Channel. Cell, 169(1), 85-92.