title: Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis.
abstract: Human ABCC1 is a member of the ATP-binding cassette (ABC) transporter superfamily, and its overexpression has been shown to cause multidrug resistance by active efflux of a wide variety of anticancer drugs. ABCC1 has been shown to exist and possibly function as a homodimer. However, a possible heterocomplex involving ABCC1 has been indicated. In this study, we performed an interactive proteomics study to examine proteins that bind to and form heterocomplexes with ABCC1 using coimmunoprecipitation and tandem mass spectrometry (MS/MS) analyses. We found that ATP synthase α binds to ABCC1 in plasma membranes with a ratio of 2:1. The ATP synthase α binding site in ABCC1 is located in the linker domain at the carboxyl core of ABCC1, and phosphorylation of the linker domain at the protein kinase A site enhances ATP synthase α binding. The interaction between ABCC1 and ATP synthase α in a heterocomplex may indicate a novel function of ABCC1 in regulating extracellular ATP level and purinergic signaling cascade.
authors.affiliation: Department of Pharmacology and Toxicology and IU Simon Cancer Center, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.
authors.forename: Youyun
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Mo
authors.forename: Raghuram
authors.initials: R
authors.lastname: Ambadipudi
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Arnold
authors.forename: Petra
authors.initials: P
authors.lastname: Hrncirova
authors.forename: Milos V
authors.initials: MV
authors.lastname: Novotny
authors.forename: Elias
authors.initials: E
authors.lastname: Georges
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results
chemical_list: D025261:Mitochondrial Proton-Translocating ATPases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1