Academic Journal
Chemically monoubiquitinated PEX5 binds to the components of the peroxisomal docking and export machinery
| العنوان: | Chemically monoubiquitinated PEX5 binds to the components of the peroxisomal docking and export machinery |
|---|---|
| المؤلفون: | Hagmann, V, Sommer, S, Fabian, P, Bierlmeier, J, van Treel, N, Mootz, H, Schwarzer, D, Azevedo, JE, Dodt, G |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | ATPases Associated with Diverse Cellular Activities / chemistry, ATPases Associated with Diverse Cellular Activities / genetics, Amino Acid Sequence / genetics, Animals, Click Chemistry, Cytosol / chemistry, Cytosol / metabolism, Fibroblasts / chemistry, Humans, Membrane Proteins / chemistry, Membrane Proteins / genetics, Mice, Molecular Docking Simulation, Mutation, Peroxisomal Targeting Signal 2 Receptor / chemistry, Peroxisomal Targeting Signal 2 Receptor / genetics, Peroxisomal Targeting Signals / genetics, Peroxisome-Targeting Signal 1 Receptor / chemistry, Peroxisome-Targeting Signal 1 Receptor / genetics, Peroxisomes / chemistry, Peroxisomes / genetics, Protein Interaction Maps / genetics, Protein Transport / genetics, Ubiquitin / chemistry, Ubiquitin / metabolism, Ubiquitination / genetics |
| الوصف: | Peroxisomal matrix proteins contain either a peroxisomal targeting sequence 1 (PTS1) or a PTS2 that are recognized by the import receptors PEX5 and PEX7, respectively. PEX5 transports the PTS1 proteins and the PEX7/PTS2 complex to the docking translocation module (DTM) at the peroxisomal membrane. After cargo release PEX5 is monoubiquitinated and extracted from the peroxisomal membrane by the receptor export machinery (REM) comprising PEX26 and the AAA ATPases PEX1 and PEX6. Here, we investigated the protein interactions of monoubiquitinated PEX5 with the docking proteins PEX13, PEX14 and the REM. “Click” chemistry was used to synthesise monoubiquitinated recombinant PEX5. We found that monoubiquitinated PEX5 binds the PEX7/PTS2 complex and restores PTS2 protein import in vivo in ¿PEX5 fibroblasts. In vitro pull-down assays revealed an interaction of recombinant PEX5 and monoubiquitinated PEX5 with PEX13, PEX14 and with the REM components PEX1, PEX6 and PEX26. The interactions with the docking proteins were independent of the PEX5 ubiquitination status whereas the interactions with the REM components were increased when PEX5 is ubiquitinated. ; We are grateful to Stephen J. Gould (Johns Hopkins University, Baltimore), Nancy E. Braverman (McGill University, Montreal), Wolfgang Schliebs (Ruhr University, Bochum) and Daniel Passon (EMBL, Hamburg) for providing plasmids and antibodies. Work in J.E.A. lab is funded by FEDER (Fundo Europeu de Desenvolvimento Regional), through COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and “The molecular mechanisms of peroxisome biogenesis” (PTDC/BEXBCM/2311/2014), and through Norte 2020 – Programa Operacional Regional do Norte, under the application of the “Porto Neurosciences and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | Scientific Reports, vol.8(1):16014; https://www.nature.com/articles/s41598-018-34200-5; https://hdl.handle.net/10216/127420 |
| DOI: | 10.1038/s41598-018-34200-5 |
| الاتاحة: | https://hdl.handle.net/10216/127420 https://doi.org/10.1038/s41598-018-34200-5 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.35F5F108 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-018-34200-5 |