Repair of CFTR Folding Defects with Correctors that Function as Pharmacological Chaperones

  • Tip W. Loo
  • David M. ClarkeEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 741)


The major cause of cystic fibrosis is the presence of processing mutations in CFTR (such as deletion of Phe-508 (F508del-CFTR)) that disrupt folding of the protein and trafficking to the cell surface. Processing mutations appear to inhibit folding of CFTR so that it accumulates in the endoplasmic reticulum as a partially folded protein. Expressing the proteins in the presence of small molecules called correctors can repair CFTR folding defects. Some correctors appear to function as pharmacological chaperones that specifically bind to the CFTR processing mutants and induce them to complete the folding process. In this chapter, we describe techniques to examine the effects of correctors on folding of CFTR processing mutants.

Key words

F508del-CFTR corrector processing mutant protein folding glycosylation disulfide cross-linking protein maturation 



This work was supported by funds from the Canadian Institutes for Health Research (Grant 62832) and the Cystic Fibrosis Foundation (Grant CLARKE08GO).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departments of Medicine and BiochemistryUniversity of TorontoTorontoCanada

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