Cited by 40Cellular transport and secretionAutophagy in Disease and TherapyFungal and yeast genetics research

Mechanistic Insights into PTS2-mediated Peroxisomal Protein Import

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Kunze, Markus, Malkani, Naila, Maurer-Stroh, Sebastian, Wiesinger, Christoph, Schmid, Johannes A., Berger, Johannes·2015·Journal of Biological Chemistry

Abstract

The destination of peroxisomal matrix proteins is encoded by short peptide sequences, which have been characterized as peroxisomal targeting signals (PTS) residing either at the C terminus (PTS1) or close to the N terminus (PTS2). PTS2-carrying proteins interact with their cognate receptor protein PEX7 that mediates their transport to peroxisomes by a concerted action with a co-receptor protein, which in mammals is the PTS1 receptor PEX5L. Using a modified version of the mammalian two-hybrid assay, we demonstrate that the interaction strength between cargo and PEX7 is drastically increased in the presence of the co-receptor PEX5L. In addition, cargo binding is a prerequisite for the interaction between PEX7 and PEX5L and ectopic overexpression of PTS2-carrying cargo protein drastically increases the formation of PEX7-PEX5L complexes in this assay. Consistently, we find that the peroxisomal transfer of PEX7 depends on cargo binding and that ectopic overexpression of cargo protein stimulates this process. Thus, the sequential formation of a highly stable trimeric complex involving cargo protein, PEX7 and PEX5L stabilizes cargo binding and is a prerequisite for PTS2-mediated peroxisomal import.

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  • Mutations affecting the long isoform of PEX5 (PEX5L) cause RCDP type 5.

    “the disease in patients with mutations specifically affecting the long isoform of PEX5, PEX5L, which is required for efficient transport of cargo-loaded PEX7 to peroxisomes [184], was designated RCDP type 5 [185].”

    From Peroxisomes in brain development and function (2016) · cites this paper as [184]

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Authors
Kunze, M., Malkani, N., Maurer-Stroh, S., Wiesinger, C., Schmid, J. A., & Berger, J.
Affiliations
Medical University of Vienna (AT)
Corresponding author
Kunze, Markus
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2015-02
Volume
290
Issue
8
Pages
4928-4940
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2115992493
Cited by
40
References
39
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 5
FWCI
1.66
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Funders
  • European Commission
  • Austrian Science Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
PtS2, peroxisomal targeting signal, peroxisomal protein import, PEX7, co-receptors, cargo binding, protein-protein interaction, peroxisomal matrix proteins, trimeric complex, two-hybrid assay
MeSH terms
Peroxisomal Targeting Signal 2 Receptor, Animals, Chlorocebus aethiops, Humans, Receptors, Cytoplasmic and Nuclear, COS Cells, Peroxisomes, Two-Hybrid System Techniques, Protein Transport, Multiprotein Complexes

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