About this item:

518 Views | 726 Downloads

Author Notes:

Correspondence: Nael A. McCarty; namccar@emory.edu

Authors' Contributions: Conceived and designed the experiments: KSR, GC, SCH and NM.

Performed the experiments: KSR and GC.

Analyzed the data: KSR and GC.

Wrote the paper: KSR and NM.

Acknowledgments: The authors thank the D. Dawson lab for providing the unpublished structure (5 ns snapshot) from their MD simulations.The authors have declared that no competing interests exist.

Disclosures: The authors have declared that no competing interests exist.


Research Funding:

This work was supported by NIH grant 5R01-DK-056481 to N.A.M. and by the Emory University Center for Respiratory Health.

Journal Title:



Volume 8, Number 9


, Pages e74574-e74574

Type of Work:

Article | Final Publisher PDF


Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), the most common life-shortening genetic disease among Caucasians. Although general features of the structure of CFTR have been predicted from homology models, the conformational changes that result in channel opening and closing have yet to be resolved. We created new closed- and open-state homology models of CFTR, and performed targeted molecular dynamics simulations of the conformational transitions in a channel opening event. The simulations predict a conformational wave that starts at the nucleotide binding domains and ends with the formation of an open conduction pathway. Changes in side-chain interactions are observed in all major domains of the protein, and experimental confirmation was obtained for a novel intra-protein salt bridge that breaks near the end of the transition. The models and simulation add to our understanding of the mechanism of ATP-dependent gating in this disease-relevant ion channel.

Copyright information:

© 2013 Rahman et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote