Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration
العنوان: | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
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المؤلفون: | Nicolae Adrian Leu, Dawei W. Dong, Junling Wang, Xuemei Han, Satoshi Kurosaka, John R. Yates, Anna Kashina, Stephanie Sterling, Virginia M.-Y. Lee, Marie E. Fina |
المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
بيانات النشر: | Nature Publishing Group UK, 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | 0301 basic medicine, Pathology, Arginyltransferase, animal diseases, lcsh:Medicine, Protein aggregation, Mass Spectrometry, Substrate Specificity, chemistry.chemical_compound, Mice, lcsh:Science, Cells, Cultured, Mice, Knockout, Neurons, Multidisciplinary, medicine.diagnostic_test, Neurodegeneration, Brain, Neurodegenerative Diseases, Aminoacyltransferases, Recombinant Proteins, Cell biology, alpha-Synuclein, medicine.medical_specialty, Proteolysis, Biology, Arginine, Models, Biological, Protein Aggregation, Pathological, Article, 03 medical and health sciences, Protein Aggregates, In vivo, Protein arginylation, medicine, Animals, Humans, Amino Acid Sequence, Alpha-synuclein, lcsh:R, medicine.disease, nervous system diseases, Disease Models, Animal, 030104 developmental biology, chemistry, nervous system, lcsh:Q, Peptides, Protein Processing, Post-Translational, Function (biology) |
الوصف: | Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn’s insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo. |
اللغة: | English |
تدمد: | 2045-2322 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac5bf5ca894ed45d2caeb45e779e3ea3 http://europepmc.org/articles/PMC5595787 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....ac5bf5ca894ed45d2caeb45e779e3ea3 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20452322 |
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