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J Biol Chem. 2017 Apr 28;292(17):6965-6977. doi: 10.1074/jbc.M116.772806. Epub 2017 Mar 3.

Peroxisomal ATP-binding cassette transporters form mainly tetramers.

Author information

1
From the Laboratoire Bio-PeroxIL EA7270 and.
2
CLIPP-ICMUB, Université Bourgogne-Franche-Comté, 6 Bd Gabriel, 21000 Dijon, France and.
3
the Drug Resistance and Membrane Proteins Team, Molecular Microbiology and Structural Biochemistry Laboratory, Institut de Biologie et Chimie des Protéines (IBCP), UMR5086 CNRS/Université Lyon 1, 7 Passage du Vercors, 69367 Lyon, France.
4
From the Laboratoire Bio-PeroxIL EA7270 and doriane.trompier@u-bourgogne.fr.

Abstract

ABCD1 and its homolog ABCD2 are peroxisomal ATP-binding cassette (ABC) half-transporters of fatty acyl-CoAs with both distinct and overlapping substrate specificities. Although it is established that ABC half-transporters have at least to dimerize to generate a functional unit, functional equivalents of tetramers (i.e. dimers of full-length transporters) have also been reported. However, oligomerization of peroxisomal ABCD transporters is incompletely understood but is of potential significance because more complex oligomerization might lead to differences in substrate specificity. In this work, we have characterized the quaternary structure of the ABCD1 and ABCD2 proteins in the peroxisomal membrane. Using various biochemical approaches, we clearly demonstrate that both transporters exist as both homo- and heterotetramers, with a predominance of homotetramers. In addition to tetramers, some larger molecular ABCD assemblies were also found but represented only a minor fraction. By using quantitative co-immunoprecipitation assays coupled with tandem mass spectrometry, we identified potential binding partners of ABCD2 involved in polyunsaturated fatty-acid metabolism. Interestingly, we identified calcium ATPases as ABCD2-binding partners, suggesting a role of ABCD2 in calcium signaling. In conclusion, we have shown here that ABCD1 and its homolog ABCD2 exist mainly as homotetramers in the peroxisomal membrane.

KEYWORDS:

ABC transporter; fatty-acid transport; peroxisome; protein assembly; protein-protein interaction

PMID:
28258215
PMCID:
PMC5409465
DOI:
10.1074/jbc.M116.772806
[Indexed for MEDLINE]
Free PMC Article

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