Cystic fibrosis: A disease of altered protein folding

Bao He Qu, Elizabeth Strickland, Philip J. Thomas

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator, CFTR. Previously we demonstrated that the common ΔF508 mutation in the first nucleotide binding domain (NBDI) alters the ability of the domain to fold into a functional three-dimensional structure, providing a molecular explanation for the observation that the mutant CFTR is retained in the endoplasmic reticulum and does not traffic to the apical membrane of affected epithelial cells. Notably, when conditions are altered to promote folding of the mutant protein, it can assume a functional conformation. Correcting the folding defect may have therapeutic benefit for the treatment of cystic fibrosis. Here we summarize these results and discuss the implications in vitro folding studies have for understanding the pathobiology of CF.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalJournal of Bioenergetics and Biomembranes
Volume29
Issue number5
DOIs
Publication statusPublished - 1997

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Keywords

  • CFTR
  • Cystic fibrosis
  • Genetic disease
  • Protein folding
  • Protein stability

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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