title: Probing substrate-induced conformational alterations in adrenoleukodystrophy protein by proteolysis.
abstract: The adrenoleukodystrophy protein (ALDP) is a half-ABC (ATP-binding cassette) transporter localized in the peroxisomal membrane. Dysfunction of this protein is the cause of the human genetic disorder X-linked adrenoleukodystrophy (X-ALD), which is characterized by accumulation of saturated, very-long-chain fatty acids (VLCFAs). This observation suggests that ALDP is involved in the metabolism of these compounds. Whether ALDP transports VLCFAs or their derivatives across the peroxisomal membrane or some cofactors essential for the efficient peroxisomal beta-oxidation of these fatty acids is still unknown. In this work, we used a protease-based approach to search for substrate-induced conformational alterations on ALDP. Our results suggest that ALDP is directly involved in the transport of long- and very-long-chain acyl-CoAs across the peroxisomal membrane.
authors.affiliation: UNILIPE, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.|Instituto de Ciências Biomédicas de Abel Salazar, Porto, Portugal.
authors.forename: Carla P
authors.initials: CP
authors.lastname: Guimarães
authors.affiliation: UNILIPE, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Clara
authors.initials: C
authors.lastname: Sá-Miranda
authors.affiliation: UNILIPE, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. jazevedo@ibmc.up.pt.|Instituto de Ciências Biomédicas de Abel Salazar, Porto, Portugal. jazevedo@ibmc.up.pt.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Azevedo
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000493:pharmacokinetics*; D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000494:pharmacology*; D020675:Peroxisomes / Q000502:physiology; D010920:Placenta / Q000737:chemistry; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D000214:Acyl Coenzyme A; D010447:Peptide Hydrolases