Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters

FEBS Letters

Holzinger, Andreas²  Mayerhofer, Peter²  Gärtner, Jutta¹  Roerig, Peter¹ 

[1]Zentrum für Kinderheilkunde, Department of Pediatrics, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany

[2]Department of Pediatrics, Ludwig Maximilians University, Lindwurmstraße 4, 80337 Munich, Germany

关键词: ATP binding cassette transporter;    Nucleotide binding fold;    Peroxisome membrane;    X-linked adrenoleukodystrophy;    Adrenoleukodystrophy protein;    70-kDa peroxisomal membrane protein;    ABC;    ATP binding cassette;    ALDP;    adrenoleukodystrophy protein;    ALDR;    ALDP-related protein;    MBP;    maltose binding protein;    PMP70;    70-kDa peroxisomal membrane protein;    P70R;    PMP70-related protein;    NBF;    nucleotide binding fold;    X-ALD;    X-linked adrenoleukodystrophy;    β-gal;    α-subunit of β-galactosidase;   

DOI  :  10.1016/S0014-5793(01)02235-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The 70-kDa peroxisomal membrane protein (PMP70) and the adrenoleukodystrophy protein (ALDP) are half ATP binding cassette (ABC) transporters in the peroxisome membrane. Mutations in the ALD gene encoding ALDP result in the X-linked neurodegenerative disorder adrenoleukodystrophy. Plausible models exist to show a role for ATP hydrolysis in peroxisomal ABC transporter functions. Here, we describe the first measurements of the rate of ATP binding and hydrolysis by purified nucleotide binding fold (NBF) fusion proteins of PMP70 and ALDP. Both proteins act as an ATP specific binding subunit releasing ADP after ATP hydrolysis; they did not exhibit GTPase activity. Mutations in conserved residues of the nucleotidases (PMP70: G478R, S572I; ALDP: G512S, S606L) altered ATPase activity. Furthermore, our results indicate that these mutations do not influence homodimerization or heterodimerization of ALDP or PMP70. The study provides evidence that peroxisomal ABC transporters utilize ATP to become a functional transporter.

【 授权许可】

Unknown