Cited by 78Cellular transport and secretionMetabolism and Genetic DisordersFungal and yeast genetics research

Function of the PEX19-binding Site of Human Adrenoleukodystrophy Protein as Targeting Motif in Man and Yeast

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Halbach, André, Lorenzen, Stephan, Landgraf, Christiane, Volkmer-Engert, Rudolf, Erdmann, Ralf, Rottensteiner, Hanspeter·2005·Journal of Biological Chemistry

Abstract

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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  1. Erdmann, R., Veenhuis, M., Mertens, D., and Kunau, W. H. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 5419 -5423
  2. Chevray, P. M., and Nathans, D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5789 -5793

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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
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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