A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.

Shani, N; Valle, D

doi:10.1073/pnas.93.21.11901

Cited by 157Metabolism and Genetic DisordersDrug Transport and Resistance MechanismsPeroxisome Proliferator-Activated Receptors

A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.

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Shani, N, Valle, D·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.21.11901PMC PMC38156

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Abstract

The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein (PMP70) are half ATP-binding cassette (ABC) transporters in the human peroxisome membrane. ALDP and PMP70 share sequence homology and both are implicated in genetic diseases. PXA1 and YKL741 are Saccharomyces cerevisiae genes that encode homologs of ALDP and PMP70. Pxa1p, a putative ortholog of ALDP, is involved in peroxisomal beta-oxidation of fatty acids while YKL741 is an open reading frame found by the yeast genome sequencing project. Here we designate YKL741 as PXA2 and show that its protein product, Pxa2p, like Pxa1p, is associated with peroxisomes but not required for their assembly. Yeast strains carrying gene disruption of PXA1, PXA2, or both have similar and, in the case of the latter, nonadditive phenotypes. We also find that the stability of Pxa1p, but not Pxa2p, is markedly reduced in the absence of the other. Finally, we find that Pxa1p and Pxa2p coimmuno-precipitate. These genetic and physical data suggest that Pxa1p and Pxa2p heterodimerize to form a complete peroxisomal ABC transporter involved in fatty acid beta-oxidation. This result predicts the presence of similar heterodimeric ABC transporters in the mammalian peroxisome membrane.

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In Saccharomyces cerevisiae, the two orthologs of ALDP, Pxa1p and Pxa2p, heterodimerize to form a functional ABC transporter.
“In the yeast Saccharomyces cerevisiae the two orthologs of ALDP, Pxa1p, and Pxa2p, heterodimerize to form a functional ABC transporter [Shani and Valle, 1996].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Shani and Valle, 1996
The paper’s opening text says Pxa1p and Pxa2p heterodimerize to form a yeast peroxisomal ABC transporter involved in fatty-acid β-oxidation. But the Discussion identifies Pxa1p as a putative ortholog of ALDP and suggests Pxa2p may instead be the yeast ortholog of PMP70. It does not support calling both proteins orthologs of ALDP. (LLM, conf=0.91)
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Self-citation

Authors: Shani, N., & Valle, D.
Affiliations: Kennedy Krieger Institute (US)
ORCID: Shani, N
Valle, D
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1996-10-15
Volume: 93
Issue: 21
Pages: 11901-11906
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.21.11901
PMC: PMC38156
OpenAlex: W2055737079
Cited by: 157
References: 42
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 6 · 2014: 2 · 2013: 6 · 2012: 3
FWCI: 8.35
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (HD10981)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-10981, P01HD010981)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: PMP70, peroxisomal membrane proteins, peroxisomal beta-oxidation, fatty acid beta-oxidation, protein stability, protein-protein interaction, Saccharomyces cerevisiae, peroxisome biogenesis
MeSH terms: ATP Binding Cassette Transporter, Subfamily D, Member 1, Adenosine Triphosphate, Fungal Proteins, Genes, Fungal, Humans, Membrane Proteins, Microbodies, Protein Binding, Saccharomyces cerevisiae, Transcription, Genetic, Open Reading Frames, ATP-Binding Cassette Transporters, Saccharomyces cerevisiae Proteins

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A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.

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