Journal article
Identification of revertants for the cystic fibrosis ΔF508 mutation using STE6-CFTR chimeras in yeast
Cell (Cambridge), Vol.73(2), pp.335-346
1993
DOI: 10.1016/0092-8674(93)90233-G
PMID: 7682896
Abstract
Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis; the most common mutation is deletion of phenylalanine at position 508 (ΔF508). We constructed STE6-CFTR chimeras with portions of the first nucleotide-binding domain (NBD1) of the yeast STE6
a-factor transporter replaced by portions of CFTR NBD1. The chimeras were functional in yeast, but mating efficiency decreased when ΔF508 was introduced into NBD1. We isolated two ΔF508 revertant mutations (R553M and R553Q) that restored mating; both were located within the CFTR NBD1 sequence. Introduction of these revertant mutations into human CFTR partially corrected the processing and CI
− channel gating defects caused by the ΔF508 mutation. These results suggest that the NBD1s of CFTR and STE6 share a similar structure and function and that, in CFTR, the regions containing F508 and R553 interact. They also indicate that the abnormal conformation produced by ΔF508 can be partially corrected by additional alterations in the protein.
Details
- Title: Subtitle
- Identification of revertants for the cystic fibrosis ΔF508 mutation using STE6-CFTR chimeras in yeast
- Creators
- John L Teem - Howard Hughes Medical Institute University of Iowa College of Medicine Department of Internal Medicine Iowa City, Iowa 52242 USAHerbert A Berger - Howard Hughes Medical Institute University of Iowa College of Medicine Department of Internal Medicine Iowa City, Iowa 52242 USALynda S Ostedgaard - Howard Hughes Medical Institute University of Iowa College of Medicine Department of Internal Medicine Iowa City, Iowa 52242 USADevra P Rich - Howard Hughes Medical Institute University of Iowa College of Medicine Department of Internal Medicine Iowa City, Iowa 52242 USALap-Chee Tsui - Department of Genetics Hospital for Sick Children Toronto, Ontario M5G 1×8 CanadaMichael J Welsh - Howard Hughes Medical Institute University of Iowa College of Medicine Department of Internal Medicine Iowa City, Iowa 52242 USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.73(2), pp.335-346
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0092-8674(93)90233-G
- PMID
- 7682896
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 1993
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020720402771
Metrics
19 Record Views