Cellular and Molecular Life Sciences

, Volume 75, Issue 20, pp 3829–3855 | Cite as

Combining theoretical and experimental data to decipher CFTR 3D structures and functions

  • Brice Hoffmann
  • Ahmad Elbahnsi
  • Pierre Lehn
  • Jean-Luc Décout
  • Fabio Pietrucci
  • Jean-Paul MornonEmail author
  • Isabelle Callebaut
Original Article


Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. These critical elements lie within membrane-spanning domains but also within NBD1 and the N-terminal extension, in which conformational plasticity is predicted to occur to help the interaction with filamin, one of the CFTR cellular partners.


CFTR ABC exporter Filamin Comparative modeling Metadynamics Cryo-electron microscopy 



This work was funded by the French Association Vaincre La Mucoviscidose (Paris). It was granted access to the HPC resources of IDRIS/CINES under the allocations 2014-077206, 2015-077206, 2016-077206, and 0020707206 made by GENCI.

Supplementary material

18_2018_2835_MOESM1_ESM.pdf (6 mb)
Supplementary material 1 (PDF 6175 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Brice Hoffmann
    • 1
    • 4
  • Ahmad Elbahnsi
    • 1
  • Pierre Lehn
    • 2
  • Jean-Luc Décout
    • 3
  • Fabio Pietrucci
    • 1
  • Jean-Paul Mornon
    • 1
    Email author
  • Isabelle Callebaut
    • 1
  1. 1.Sorbonne Université, Muséum National d’Histoire Naturelle, UMR CNRS 7590, IRD, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMCParisFrance
  2. 2.INSERM U1078, SFR ScInBioS, Université de Bretagne OccidentaleBrestFrance
  3. 3.CNRS UMR5063, Université Grenoble-AlpesGrenobleFrance
  4. 4.IktosParisFrance

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