Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis

J Proteome Res. 2012 Feb 3;11(2):1364-72. doi: 10.1021/pr201003g. Epub 2012 Jan 18.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Mitochondrial Proton-Translocating ATPases / chemistry
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Multidrug Resistance-Associated Proteins / chemistry
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Mapping / methods
  • Proteomics / methods
  • Reproducibility of Results


  • Multidrug Resistance-Associated Proteins
  • Mitochondrial Proton-Translocating ATPases
  • multidrug resistance-associated protein 1