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Julien Micoud

Interdomains interactions roles in CFTR protein

Published on 2 July 2008


Thesis presented July 02, 2008

Abstract:
CFTR is a chloride channel which belongs to the ABC transporters superfamily. This protein is composed of 5 domains: 2 nucleotide binding domains (NBD), 2 transmembrane domains (TMD), and a regulatory one. Interactions between these different domains are essentials for numerous processes, including folding, maturation and function of CFTR. However, the roles of these domains and the nature of their interaction in biogenesis, folding, maturatio​n, function and stability at the plasma membrane are still unknown.
In order to precise these roles, we have studied the intracellular comportment of genetically modified CFTR proteins. Our results confirmed that contrary to NBD2, NBD1 is essential for the maturation and for the intracellular trafficking of CFTR. NBD2 is not important for the folding of the protein, but we point out for the first time its necessity for the stability of CFTR at the plasma membrane.
In an other part of this work, we have shown that the 6th transmembrane segment is not stable in the plasma membrane et must be important for folding of the protein, probably by its implication in the packing of the TMDs.

Keywords:
CFTR, NBD, TMD, maturation, stability, domain, interaction

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