Generating Symmetry in the Asymmetric ATP-binding Cassette (ABC) Transporter Pdr5 from Saccharomyces cerevisiae
| Autor: | Nils Hanekop, Lutz Schmitt, Petra Kueppers, Rakeshkumar P. Gupta |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
ATP Binding Cassette Transporter
Subfamily B Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae ATP-binding cassette transporter Biology Biochemistry Structure-Activity Relationship chemistry.chemical_compound Adenosine Triphosphate ATP hydrolysis Membrane Biology Humans ATP Binding Cassette Transporter Subfamily B Member 1 Binding site Molecular Biology ATP-binding domain of ABC transporters P-glycoprotein Binding Sites Cell Membrane food and beverages Biological Transport Cell Biology Membrane transport biology.organism_classification Drug Resistance Multiple Kinetics chemistry Mutagenesis embryonic structures biology.protein ATP-Binding Cassette Transporters Adenosine triphosphate |
| Zdroj: | Journal of Biological Chemistry. 289:15272-15279 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.553065 |
| Popis: | Pdr5 is a plasma membrane-bound ABC transporter from Saccharomyces cerevisiae and is involved in the phenomenon of resistance against xenobiotics, which are clinically relevant in bacteria, fungi, and humans. Many fungal ABC transporters such as Pdr5 display an inherent asymmetry in their nucleotide-binding sites (NBS) unlike most of their human counterparts. This degeneracy of the NBSs is very intriguing and needs explanation in terms of structural and functional relevance. In this study, we mutated nonconsensus amino acid residues in the NBSs to its consensus counterpart and studied its effect on the function of the protein and effect on yeast cells. The completely "regenerated" Pdr5 protein was severely impaired in its function of ATP hydrolysis and of rhodamine 6G transport. Moreover, we observe alternative compensatory mechanisms to counteract drug toxicity in some of the mutants. In essence, we describe here the first attempts to restore complete symmetry in an asymmetric ABC transporter and to study its effects, which might be relevant to the entire class of asymmetric ABC transporters. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|