iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations
| العنوان: | iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations |
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| المؤلفون: | Søren W Gersting, Caroline C. Friedel, Philipp Guder, Stephan Kemp, Anja Schultze, Julian M Klingbeil, Amelie S. Lotz-Havla, Ania C. Muntau, Ralf Zimmer, Ralf Erdmann, Ana-Maria Bulau, Mathias Woidy, Ilona Dahmen, Heidi Noll-Puchta |
| المساهمون: | Laboratory Genetic Metabolic Diseases, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Gastroenterology Endocrinology Metabolism |
| المصدر: | Journal of proteome research, 20(9), 4366-4380. American Chemical Society |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | X-ALD, Informatics, lipid droplets, interactome, Computational biology, Biology, medicine.disease_cause, ATP Binding Cassette Transporter, Subfamily D, Member 1, fatty acids, Biochemistry, Interactome, Protein–protein interaction, protein-protein interaction, PEX10, FAR1, Interaction network, medicine, Animals, Mutation, screening, ABCD1, General Chemistry, Peroxisome, medicine.disease, Phenotype, Energy Transfer, bioluminescence resonance energy transfer, ATP-Binding Cassette Transporters, BRET, Adrenoleukodystrophy, living cells |
| الوصف: | Mapping the network of proteins provides a powerful means to investigate the function of disease genes and to unravel the molecular basis of phenotypes. We present an automated informatics-aided and bioluminescence resonance energy transfer-based approach (iBRET) enabling high-confidence detection of protein-protein interactions in living mammalian cells. A screen of the ABCD1 protein, which is affected in X-linked adrenoleukodystrophy (X-ALD), against an organelle library of peroxisomal proteins demonstrated applicability of iBRET for large-scale experiments. We identified novel protein-protein interactions for ABCD1 (with ALDH3A2, DAO, ECI2, FAR1, PEX10, PEX13, PEX5, PXMP2, and PIPOX), mapped its position within the peroxisomal protein-protein interaction network, and determined that pathogenic missense variants in ABCD1 alter the interaction with selected binding partners. These findings provide mechanistic insights into pathophysiology of X-ALD and may foster the identification of new disease modifiers. |
| تدمد: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.1c00330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95ad52d8470a060cc81d7c785d0d7557 https://doi.org/10.1021/acs.jproteome.1c00330 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....95ad52d8470a060cc81d7c785d0d7557 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15353907 15353893 |
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| DOI: | 10.1021/acs.jproteome.1c00330 |