Evidence map›Paper›PMID 23902771›Full record

ArticleThe Journal of biological chemistry2013

Redox-regulated cargo binding and release by the peroxisomal targeting signal receptor, Pex5.

Changle Ma, Danielle Hagstrom, Soumi Guha Polley, Suresh Subramani

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed.

  1. Macrophage peroxisomes at the crossroads of inflammation.Immunometabolism (Cobham, Surrey) · 2026
    Review
  2. Building peroxisomes: perspectives on plant peroxins.Biochemical Society transactions · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022
    Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Changle MaSection of Molecular Biology, Division of Biological Sciences, University California, San Diego, La Jolla, California 92093-0322.
Danielle HagstromSection of Molecular Biology, Division of Biological Sciences, University California, San Diego, La Jolla, California 92093-0322.
Soumi Guha PolleySection of Molecular Biology, Division of Biological Sciences, University California, San Diego, La Jolla, California 92093-0322.
Suresh SubramaniSection of Molecular Biology, Division of Biological Sciences, University California, San Diego, La Jolla, California 92093-0322. Electronic address: ssubramani@ucsd.edu.

Funding

TARGETING OF PROTEINS INTO PEROXISOMESR01DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AITCHISON, JOHN D., SUBRAMANI, SURESH · 1990 to 2025
$8.4M
Targeting of proteins into peroxisomesR37DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANI, SURESH · 2004 to 2013
$5.3M
Targeting of Proteins into PeroxisomesR56DK041737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANI, SURESH · 2014 to 2014
$149k
NIDDK NIH HHS DK41737NIDDK NIH HHS R01 DK041737NIDDK NIH HHS R37 DK041737NIDDK NIH HHS R56 DK041737
6 · The paper itself

Abstract

In its role as a mobile receptor for peroxisomal matrix cargo containing a peroxisomal targeting signal called PTS1, the protein Pex5 shuttles between the cytosol and the peroxisome lumen. Pex5 binds PTS1 proteins in the cytosol via its C-terminal tetratricopeptide domains and delivers them to the peroxisome lumen, where the receptor·cargo complex dissociates. The cargo-free receptor is exported to the cytosol for another round of import. How cargo release and receptor recycling are regulated is poorly understood. We found that Pex5 functions as a dimer/oligomer and that its protein interactions with itself (homo-oligomeric) and with Pex8 (hetero-oligomeric) control the binding and release of cargo proteins. These interactions are controlled by a redox-sensitive amino acid, cysteine 10 of Pex5, which is essential for the formation of disulfide bond-linked Pex5 forms, for high affinity cargo binding, and for receptor recycling. Disulfide bond-linked Pex5 showed the highest affinity for PTS1 cargo. Upon reduction of the disulfide bond by dithiothreitol, Pex5 transitioned to a noncovalent dimer, concomitant with the partial release of PTS1 cargo. Additionally, dissipation of the redox balance between the cytosol and the peroxisome lumen caused an import defect. A hetero-oligomeric interaction between the N-terminal domain (amino acids 1-110) of Pex5 and a conserved motif at the C terminus of Pex8 further facilitates cargo release, but only under reducing conditions. This interaction is also important for the release of PTS1 proteins. We suggest a redox-regulated model for Pex5 function during the peroxisomal matrix protein import cycle.

Indexed as

Protein MultimerizationAmino Acid MotifsFungal ProteinsOxidation-ReductionPeroxisomesPeroxisome-Targeting Signal 1 ReceptorPichiaProtein BindingProtein Structure, TertiaryReceptors, Cytoplasmic and NuclearFungal ProteinsPeroxisome-Targeting Signal 1 ReceptorPEX5 protein, Pichia pastorisReceptors, Cytoplasmic and NuclearDisulfide BondingPeroxisomesPichia pastorisProtein TranslocationPTS1 ReceptorReceptor RecyclingRedox RegulationYeast

Identifiers

PMID23902771
PMCPMC3779719

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.