Complement yourself: Transcomplementation rescues partially folded mutant proteins

Research output: Contribution to journalArticle

Abstract

Cystic fibrosis (CF) is an autosomal disease associated with malfunction in fluid and electrolyte transport across several mucosal membranes. The most common mutation in CF is an in-frame three-base pair deletion that removes a phenylalanine at position 508 in the first nucleotide-binding domain of the cystic fibrosis conductance regulator (CFTR) chloride channel. This mutation has been studied extensively and leads to biosynthetic arrest of the protein in the endoplasmic reticulum and severely reduced channel activity. This review discusses a novel method of rescuing ΔF508 with transcomplementation, which occurs when smaller fragments of CFTR containing the wild-type nucleotide binding domain are co-expressed with the F508 deletion mutant. Transcomplementation rescues the processing and channel activity of ΔF508 and reduces its rate of degradation in airway epithelial cells. To apply transcomplementation as a therapy would require that the cDNA encoding the truncated CFTR be delivered to cells. We also discuss a gene therapeutic approach based on delivery of a truncated form of CFTR to airway cells using adeno-associated viral vectors.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalBiophysical Reviews
Volume6
Issue number1
DOIs
StatePublished - Mar 2014

Fingerprint

Mutant Proteins
Cystic Fibrosis
Nucleotides
Mutation
Chloride Channels
Phenylalanine
Recombinant Proteins
Base Pairing
Endoplasmic Reticulum
Electrolytes
Complementary DNA
Epithelial Cells
Membranes
Therapeutics
Genes

Keywords

  • CFTR
  • Degradation
  • Endoplasmic reticulum
  • Mutants
  • Transcomplementation

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology
  • Structural Biology

Cite this

Complement yourself : Transcomplementation rescues partially folded mutant proteins. / Cebotaru, Liudmila; Guggino, William B.

In: Biophysical Reviews, Vol. 6, No. 1, 03.2014, p. 169-180.

Research output: Contribution to journalArticle

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