Mechanistic Insights into PTS2-mediated Peroxisomal Protein Import
Open accessAbstract
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)
- PMC
- PMC4335231
- 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
- hybrid
- doi.org
- Licence
- 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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