A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein

Mark S Szczypka; John A Wemmie; W Scott Moye-Rowley; Dennis J Thiele

doi:10.1016/S0021-9258(17)31723-4

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A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein

Journal article

Open access

Peer reviewed

A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein

Mark S Szczypka, John A Wemmie, W Scott Moye-Rowley and Dennis J Thiele

The Journal of biological chemistry, Vol.269(36), pp.22853-22857

09/09/1994

DOI: 10.1016/S0021-9258(17)31723-4

PMID: 7521334

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Abstract

Members of the ATP binding cassette (ABC) protein superfamily transport a variety of substances across biological membranes, including drugs, ions, and peptides. The yeast cadmium factor (YCF1) gene from Saccharomyces cerevisiae is required for cadmium resistance and encodes a 1,515 amino acid protein with extensive homology to both the human multidrug resistance-associated protein (MRP1) and the cystic fibrosis transmembrane conductance regulator (hCFTR). S. cerevisiae cells harboring a deletion of the YCF1 gene are hypersensitive to cadmium compared with wild type cells. Mutagenesis experiments demonstrate that conserved amino acid residues, functionally critical in hCFTR, play a vital role in YCF1-mediated cadmium resistance. Mutagenesis of phenylalanine 713 in the YCF1 nucleotide binding fold 1, which correlates with the delta F508 mutation found in the most common form of cystic fibrosis, completely abolished YCF1 function in cadmium detoxification. Furthermore, substitution of a serine to alanine residue in a potential protein kinase A phosphorylation site in a central region of YCF1, which displays sequence similarity to the central regulatory domain of hCFTR, also rendered YCF1 nonfunctional. These results suggest that YCF1 is composed of modular domains found in human proteins which function in drug and ion transport.

Gene Expression

Mutagenesis

Phenotype

Polymerase Chain Reaction

Fungal Proteins - biosynthesis

Saccharomyces cerevisiae - genetics

Humans

Molecular Sequence Data

Saccharomyces cerevisiae - drug effects

Drug Resistance, Microbial - genetics

ATP-Binding Cassette, Sub-Family B, Member 1

Cystic Fibrosis Transmembrane Conductance Regulator

Saccharomyces cerevisiae - metabolism

Base Sequence

Gene Deletion

Genes, Fungal

Drosophila - genetics

Amino Acid Sequence

Cadmium - toxicity

Membrane Proteins - genetics

Fungal Proteins - genetics

DNA Primers

Membrane Glycoproteins - genetics

Sequence Homology, Amino Acid

Carrier Proteins - genetics

Drug Resistance - genetics

ATP-Binding Cassette Transporters

Animals

Cystic Fibrosis - genetics

Saccharomyces cerevisiae Proteins

Details

Title: Subtitle: A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein
Creators: Mark S Szczypka - Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606
John A Wemmie
W Scott Moye-Rowley
Dennis J Thiele
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.269(36), pp.22853-22857
DOI: 10.1016/S0021-9258(17)31723-4
PMID: 7521334
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: GM41840 / NIGMS NIH HHS M01-RR00042 / NCRR NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 09/09/1994
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984003449802771

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