Journal article
Regulation by ATP and ADP of CFTR Chloride Channels That Contain Mutant Nucleotide-Binding Domains
Science (American Association for the Advancement of Science), Vol.257(5077), pp.1701-1704
09/18/1992
DOI: 10.1126/science.1382316
PMID: 1382316
Abstract
Regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is unusual in that phosphorylated channels require cytosolic adenosine triphosphate (ATP) to open. The CFTR contains two regions predicted to be nucleotide-binding domains (NBDs); site-directed mutations in each NBD have now been shown to alter the relation between ATP concentration and channel activity, which indicates that ATP stimulates the channel by direct interaction with both NBDs. The two NBDs are not, however, functionally equivalent: adenosine diphosphate (ADP) competitively inhibited the channel by interacting with NBD2 but not by interacting with NBD1. Four cystic fibrosis-associated mutations in the NBDs reduced absolute chloride channel activity, and one mutation also decreased the potency with which ATP stimulates channel activity. Dysfunction of ATP-dependent stimulation through the NBDs may be the basis for defective CFTR chloride channel activity in some cystic fibrosis patients.
Details
- Title: Subtitle
- Regulation by ATP and ADP of CFTR Chloride Channels That Contain Mutant Nucleotide-Binding Domains
- Creators
- Matthew P. Anderson - University of IowaMichael J. Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.257(5077), pp.1701-1704
- DOI
- 10.1126/science.1382316
- PMID
- 1382316
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Language
- English
- Date published
- 09/18/1992
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984259443902771
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