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- Title
Molecular models of the open and closed states of the whole human CFTR protein.
- Authors
Mornon, Jean-Paul; Lehn, Pierre; Callebaut, Isabelle
- Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR), involved in cystic fibrosis (CF), is a chloride channel belonging to the ATP-binding cassette (ABC) superfamily. Using the experimental structure of Sav1866 as template, we previously modeled the human CFTR structure, including membrane-spanning domains (MSD) and nucleotide-binding domains (NBD), in an outward-facing conformation (open channel state). Here, we constructed a model of the CFTR inward-facing conformation (closed channel) on the basis of the recent corrected structures of MsbA and compared the structural features of those two states of the channel. Interestingly, the MSD:NBD coupling interfaces including F508 (DeltaF508 being the most common CF mutation) are mainly left unchanged. This prediction, completed by the modeling of the regulatory R domain, is supported by experimental data and provides a molecular basis for a better understanding of the functioning of CFTR, especially of the structural features that make CFTR the unique channel among the ABC transporters.
- Publication
Cellular and molecular life sciences : CMLS, 2009, Vol 66, Issue 21, p3469
- ISSN
1420-9071
- Publication type
Journal Article
- DOI
10.1007/s00018-009-0133-0