RGD Reference Report - Structure-function analysis of peroxisomal ATP-binding cassette transporters using chimeric dimers. - Rat Genome Database

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Structure-function analysis of peroxisomal ATP-binding cassette transporters using chimeric dimers.

Authors: Geillon, Flore  Gondcaille, Catherine  Charbonnier, Soëli  Van Roermund, Carlo W  Lopez, Tatiana E  Dias, Alexandre M M  Pais de Barros, Jean-Paul  Arnould, Christine  Wanders, Ronald J  Trompier, Doriane  Savary, Stéphane 
Citation: Geillon F, etal., J Biol Chem. 2014 Aug 29;289(35):24511-20. doi: 10.1074/jbc.M114.575506. Epub 2014 Jul 20.
RGD ID: 13673760
Pubmed: PMID:25043761   (View Abstract at PubMed)
PMCID: PMC4148876   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M114.575506   (Journal Full-text)

ABCD1 and ABCD2 are two closely related ATP-binding cassette half-transporters predicted to homodimerize and form peroxisomal importers for fatty acyl-CoAs. Available evidence has shown that ABCD1 and ABCD2 display a distinct but overlapping substrate specificity, although much remains to be learned in this respect as well as in their capability to form functional heterodimers. Using a cell model expressing an ABCD2-EGFP fusion protein, we first demonstrated by proximity ligation assay and co-immunoprecipitation assay that ABCD1 interacts with ABCD2. Next, we tested in the pxa1/pxa2¿ yeast mutant the functionality of ABCD1/ABCD2 dimers by expressing chimeric proteins mimicking homo- or heterodimers. For further structure-function analysis of ABCD1/ABCD2 dimers, we expressed chimeric dimers fused to enhanced GFP in human skin fibroblasts of X-linked adrenoleukodystrophy patients. These cells are devoid of ABCD1 and accumulate very long-chain fatty acids (C26:0 and C26:1). We checked that the chimeric proteins were correctly expressed and targeted to the peroxisomes. Very long-chain fatty acid levels were partially restored in transfected X-linked adrenoleukodystrophy fibroblasts regardless of the chimeric construct used, thus demonstrating functionality of both homo- and heterodimers. Interestingly, the level of C24:6 n-3, the immediate precursor of docosahexaenoic acid, was decreased in cells expressing chimeric proteins containing at least one ABCD2 moiety. Our data demonstrate for the first time that both homo- and heterodimers of ABCD1 and ABCD2 are functionally active. Interestingly, the role of ABCD2 (in homo- and heterodimeric forms) in the metabolism of polyunsaturated fatty acids is clearly evidenced, and the chimeric dimers provide a novel tool to study substrate specificity of peroxisomal ATP-binding cassette transporters.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcd1Ratvery long-chain fatty acid catabolic process involved_inIMP PMID:25043761UniProt 
Abcd2Ratvery long-chain fatty acid catabolic process involved_inIMP PMID:25043761UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcd1Ratperoxisome located_inIDA PMID:25043761UniProt 
Abcd2Ratperoxisome located_inIDA PMID:25043761UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcd1Ratprotein binding enablesIPIUniProtKB:Q9QY44PMID:25043761UniProt 
Abcd2Ratprotein binding enablesIPIUniProtKB:D3ZHR2PMID:25043761UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Abcd1  (ATP binding cassette subfamily D member 1)
Abcd2  (ATP binding cassette subfamily D member 2)


Additional Information