title: Peroxisomal ATP-binding cassette transporters form mainly tetramers.
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.
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and.
authors.forename: Flore
authors.initials: F
authors.lastname: Geillon
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gondcaille
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Raas
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and.
authors.forename: Alexandre M M
authors.initials: AMM
authors.lastname: Dias
authors.affiliation: CLIPP-ICMUB, Université Bourgogne-Franche-Comté, 6 Bd Gabriel, 21000 Dijon, France and.
authors.forename: Delphine
authors.initials: D
authors.lastname: Pecqueur
authors.affiliation: CLIPP-ICMUB, Université Bourgogne-Franche-Comté, 6 Bd Gabriel, 21000 Dijon, France and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Truntzer
authors.affiliation: CLIPP-ICMUB, Université Bourgogne-Franche-Comté, 6 Bd Gabriel, 21000 Dijon, France and.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Lucchi
authors.affiliation: CLIPP-ICMUB, Université Bourgogne-Franche-Comté, 6 Bd Gabriel, 21000 Dijon, France and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ducoroy
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Falson
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Savary
authors.affiliation: From the Laboratoire Bio-PeroxIL EA7270 and doriane.trompier@u-bourgogne.fr.
authors.forename: Doriane
authors.initials: D
authors.lastname: Trompier
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D020675:Peroxisomes / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: C000621132:ABCD1 protein, rat; C508354:ABCD2 protein, mouse; D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C552836:Abcd1 protein, mouse; C525916:Abcd2 protein, rat; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases
keywords: ABC transporter; fatty-acid transport; peroxisome; protein assembly; protein-protein interaction