ΔF508 mutation increases conformational flexibility of CFTR protein
نویسندگان
چکیده
منابع مشابه
Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.
Most cystic fibrosis is caused by the deletion of a single amino acid (F508) from CFTR and the resulting misfolding and destabilization of the protein. Compounds identified by high-throughput screening to improve ΔF508 CFTR maturation have already entered clinical trials, and it is important to understand their mechanisms of action to further improve their efficacy. Here, we showed that several...
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Deletion of Phe508 (DeltaF508) in the first nucleotide-binding domain (NBD1) of CFTR causes cystic fibrosis. The mutation severely reduces the stability and folding of the protein by disrupting interactions between NBD1 and the second transmembrane domain (TMD2). We found that replacement of Val510 with acidic residues (but not neutral or positive residues) promoted maturation of DeltaF508-CFTR...
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» A noticeable weakness of discovered corrector molecules is the lack of convincing data on their mechanism of action which is pivotal to understand their limited clinical efficacy and critical to rationally develop the next generation of correctors with improved activity. « Cystic fibrosis (CF) is one of the most prevalent life‐threatening autosomal recessive disorders in the Western World, wi...
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The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and c...
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ژورنال
عنوان ژورنال: Journal of Cystic Fibrosis
سال: 2008
ISSN: 1569-1993
DOI: 10.1016/j.jcf.2007.11.008