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Rôles des interactions interdomaines dans le comportement cellulaire de la protéine CFTR

Abstract : Deletion of Phe-508 (Delta F508) in the NBD1 of CFTR, an ABC chloride channel protein, causes its retention in the endoplasmic reticulum (ER) by preventing its conformational maturation without altering profoundly the local structure of NBD1, but possibly by disrupting the interaction between NBD1, NBD2, TMD1 and/or TMD2. However, the individual role of each domain in biogenesis, folding, maturation and membrane stability of a full length CFTR is still under debate. Using biochemistry, molecular and cellular biology methods, we demonstrate for the first time that each CFTR domain has a specific role. Our results showed that intact NBD1 at its N-terminal position is important in maturation and folding processes compared to NBD2 that was mandatory for CFTR function and membrane stability. The later was not affected by the CFTR folding state. Finally, TMD1 transmembrane segment 6 (S6) did not affect CFTR lipid bilayer orientation but did stop its maturation, suggesting the implication of S6 in CFTR domains interaction that is necessary for its normal cellular behaviour. Together, our results showed that CFTR folding is tightly depending on its domains interaction.
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Contributor : Julien Micoud <>
Submitted on : Sunday, February 22, 2009 - 3:23:08 PM
Last modification on : Wednesday, November 4, 2020 - 2:10:59 PM
Long-term archiving on: : Tuesday, June 8, 2010 - 10:47:30 PM


  • HAL Id : tel-00363323, version 1



Julien Micoud. Rôles des interactions interdomaines dans le comportement cellulaire de la protéine CFTR. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00363323⟩



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