Function of the PEX19-binding Site of Human Adrenoleukodystrophy Protein as Targeting Motif in Man and Yeast
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We predicted in human peroxisomal membrane proteins (PMPs) the binding sites for PEX19, a key player in the topogenesis of PMPs, by virtue of an algorithm developed for yeast PMPs. The best scoring PEX19-binding site was found in the adrenoleukodystrophy protein (ALDP). The identified site was indeed bound by human PEX19 and was also recognized by the orthologous yeast PEX19 protein. Likewise, both human and yeast PEX19 bound with comparable affinities to the PEX19-binding site of the yeast PMP Pex13p. Interestingly, the identified PEX19-binding site of ALDP coincided with its previously determined targeting motif. We corroborated the requirement of the ALDP PEX19-binding site for peroxisomal targeting in human fibroblasts and showed that the minimal ALDP fragment targets correctly also in yeast, again in a PEX19-binding site-dependent manner. Furthermore, the human PEX19-binding site of ALDP proved interchangeable with that of yeast Pex13p in an in vivo targeting assay. Finally, we showed in vitro that most of the predicted binding sequences of human PMPs represent true binding sites for human PEX19, indicating that human PMPs harbor common PEX19-binding sites that do resemble those of yeast. Our data clearly revealed a role for PEX19-binding sites as PMP-targeting motifs across species, thereby demonstrating the evolutionary conservation of PMP signal sequences from yeast to man.
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The very N-terminal part of ABCD1 precedes the PEX19 binding site, which is required for proper peroxisomal targeting of ABCD1.
“The very N-terminal part of the protein precedes the PEX19 binding site, which is required for proper peroxisomal targeting of ABCD1.78”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [78]
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- Authors
- Halbach, A., Lorenzen, S., Landgraf, C., Volkmer-Engert, R., Erdmann, R., & Rottensteiner, H.
- Affiliations
- Ruhr University Bochum (DE)
- Institute of Biochemistry (CH)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Halbach, André
- Erdmann, Ralf
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 280
- Issue
- 22
- Pages
- 21176-21182
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2044270028
- Cited by
- 78
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 6 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 7
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Commission (LSHG-CT-2004-512018)
- Deutsche Forschungsgemeinschaft (SFB 480)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- PEX19, peroxisomal membrane proteins, peroxisomal targeting, signal peptide, evolutionary conservation, peroxisome biogenesis
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Algorithms, Binding Sites, Cytosol, Escherichia coli, Fibroblasts, Humans, Kinetics, Membrane Proteins, Oligonucleotides, Peptides, Plasmids, Protein Binding, Saccharomyces cerevisiae, Signal Transduction, DNA, Complementary, ATP-Binding Cassette Transporters, Evolution, Molecular, Two-Hybrid System Techniques, Amino Acid Motifs, Green Fluorescent Proteins
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