Alternate Translation Initiation Codons Can Create Functional Forms of Cystic Fibrosis Transmembrane Conductance Regulator

To evaluate the function of transmembrane domain 1 (TMD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) and the methionines that function in translation initiation, a series of progressive 5’ truncations in TMD1 were created to coincide with residues that might serve as translati...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-05, Vol.270 (20), p.11941-11946
Main Authors: Carroll, Tiziana Piazza, Morales, Marcelo M., Fulmer, Stephanie B., Allen, Sandra S., Flotte, Terence R., Cutting, Garry R., Guggino, William B.
Format: Article
Language:English
Subjects:
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology
Animals
Base Sequence
Chloride Channels - biosynthesis
Chloride Channels - chemistry
Chloride Channels - genetics
Chloride Channels - metabolism
Codon - genetics
Cystic Fibrosis - genetics
Cystic Fibrosis Transmembrane Conductance Regulator
Humans
Ion Channel Gating - drug effects
Membrane Proteins - biosynthesis
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Molecular Sequence Data
Oocytes
Patch-Clamp Techniques
Peptide Chain Initiation, Translational
Protein Structure, Tertiary
Recombinant Fusion Proteins - biosynthesis
Sequence Deletion
Structure-Activity Relationship
Xenopus
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Summary:To evaluate the function of transmembrane domain 1 (TMD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) and the methionines that function in translation initiation, a series of progressive 5’ truncations in TMD1 were created to coincide with residues that might serve as translation initiation codons. Expression of the mutants in Xenopus oocytes demonstrated that internal sites in TMD1 can function as initiation codons. In addition, all of the mutants that progressively removed the first four transmembrane segments (M1-M4) of TMD1 expressed functional cAMP-regulated Cl- channels with ion selectivity identical to wild-type CFTR but with reduced open probability and single channel conductance. Further removal of transmembrane segments did not produce functional Cl- channels. These data suggest that segments M1-M4 are not essential components of the conduction pore or the selectivity filter of CFTR.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.20.11941