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Altered protein folding may be the molecular basis of most cases of cystic fibrosis
Author(s) -
Thomas Philip J.,
Ko Young H.,
Pedersen Peter L.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81399-7
Subject(s) - cystic fibrosis , cystic fibrosis transmembrane conductance regulator , mutant , mutation , transmembrane protein , protein folding , δf508 , folding (dsp implementation) , potentiator , chemistry , regulator , membrane protein , microbiology and biotechnology , biology , genetics , membrane , biochemistry , gene , receptor , engineering , electrical engineering
Experiments have demonstrated that the cystic fibrosis transmembrane conductance regulator protein (CFTR), containing the most common cystic fibrosis (CF)‐causing mutation (ΔF508), reaches the plasma membrane in reduced amounts. Studies of a peptide model of CFTR indicate that the ΔF508 mutated region is more sensitive to denaturating conditions. This paper proposes that altered protein folding accounts for these findings, and, thus, most cases of CF. Significantly, the hypothesis makes specific predictions about the effect of stabilizing conditions on mutant CFTR, and, further, suggests a new class of pharmaceuticals that may prove effective in the treatment of this important genetic disease.