دورية أكاديمية
The peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo
| العنوان: | The peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo |
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| المؤلفون: | Dias, AF, Rodrigues, TA, Pedrosa, AG, Barros-Barbosa, A, Francisco, T, Azevedo, JE |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology |
| سنة النشر: | 2017 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | Amino Acid Motifs, Amino Acid Substitution, Biological Transport, Endopeptidase K/metabolism, Gene Deletion, Humans, Hydrogen-Ion Concentration, Intracellular Membranes/metabolism, Membrane Proteins/chemistry, Membrane Proteins/genetics, Membrane Proteins/metabolism, Models, Biological, Mutagenesis, Site-Directed, Mutation, Missense, Peptide Fragments/chemistry, Peptide Fragments/genetics, Peptide Fragments/metabolism, Peroxisome-Targeting Signal 1 Receptor, Peroxisomes/metabolism, Protein Interaction Domains and Motifs, Protein Multimerization, Receptors, Cytoplasmic and Nuclear/chemistry, Cytoplasmic and Nuclear/genetics, Cytoplasmic and Nuclear/metabolism, Recombinant Fusion Proteins/chemistry, Recombinant Fusion Proteins/metabolism |
| الوصف: | A remarkable property of the machinery for import of peroxisomal matrix proteins is that it can accept already folded proteins as substrates. This import involves binding of newly synthesized proteins by cytosolic peroxisomal biogenesis factor 5 (PEX5) followed by insertion of the PEX5– cargo complex into the peroxisomal membrane at the docking/translocation module (DTM). However, how these processes occur remains largely unknown. Here, we used truncated PEX5 molecules to probe the DTM architecture. We found that the DTM can accommodate a larger number of truncated PEX5 molecules comprising amino acid residues 1–197 than full-length PEX5 molecules. A shorter PEX5 version (PEX5(1–125)) still interacted correctly with the DTM; however, this species was largely accessible to exoge-nously added proteinase K, suggesting that this protease can access the DTM occupied by a small PEX5 protein. Interestingly, the PEX5(1–125)–DTM interaction was inhibited by a polypeptide comprising PEX5 residues 138 – 639. Apparently, the DTM can recruit soluble PEX5 through interactions with different PEX5 domains, suggesting that the PEX5–DTM interactions are to some degree fuzzy. Finally, we found that the interaction between PEX5 and PEX14, a major DTM component, is stable at pH 11.5. Thus, there is no reason to assume that the hitherto intriguing resistance of DTM-bound PEX5 to alkaline extraction reflects its direct contact with the peroxisomal lipid bilayer. Collectively, these results suggest that the DTM is best described as a large cavity-forming protein assembly into which cytosolic PEX5 can enter to release its cargo. ; This work was supported in part by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operational Pro-gramme for Competitiveness and Internationalization (POCI), Portugal 2020 and by Portuguese funds through Fundação para a Ciência e a Tec-nologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0021-9258 |
| العلاقة: | Journal of Biological Chemistry, vol.292(37), p. 15287-15300; http://www.jbc.org/content/292/37/15287.longTest; https://repositorio-aberto.up.pt/handle/10216/117912Test |
| DOI: | 10.1074/jbc.M117.805044 |
| الإتاحة: | https://doi.org/10.1074/jbc.M117.805044Test https://repositorio-aberto.up.pt/handle/10216/117912Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BFAE2A64 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219258 |
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| DOI: | 10.1074/jbc.M117.805044 |