Tilted properties of the 67-78 fragment of α-synuclein are responsible for membrane destabilization and neurotoxicity
| العنوان: | Tilted properties of the 67-78 fragment of α-synuclein are responsible for membrane destabilization and neurotoxicity |
|---|---|
| المؤلفون: | Benoit Charloteaux, Benaiessa Elmoualija, Laurence Lins, Aurélien Lorin, Jean-Marc Crowet, Ernst Heinen, Ingrid Dupiereux, Robert Brasseur, Vincent Stroobant |
| المساهمون: | CBMN gembloux |
| المصدر: | Proteins: Structure, Function, and Bioinformatics Proteins: Structure, Function, and Bioinformatics, 2007, 68 (4), pp.936-947. ⟨10.1002/prot.21483⟩ |
| بيانات النشر: | HAL CCSD, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Models, Molecular, Protein Conformation, Sequence analysis, animal diseases, Neurotoxins, Mutant, Peptide, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, Structural Biology, mental disorders, medicine, Humans, Molecular Biology, Phospholipids, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Alpha-synuclein, chemistry.chemical_classification, 0303 health sciences, Liposome, Circular Dichroism, 030302 biochemistry & molecular biology, Wild type, Neurotoxicity, Parkinson Disease, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Peptide Fragments, nervous system diseases, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, nervous system, chemistry, alpha-Synuclein, Biophysics, Lewy Bodies, Stress, Mechanical |
| الوصف: | Alpha-synuclein is a 140 residue protein associated with Parkinson's disease. Intraneural inclusions called Lewy bodies and Lewy neurites are mainly composed of alpha-synuclein aggregated into amyloid fibrils. Other amyloidogenic proteins, such as the beta amyloid peptide involved in Alzheimer's disease and the prion protein (PrP) associated with Creuztfeldt-Jakob's disease, are known to possess "tilted peptides". These peptides are short protein fragments that adopt an oblique orientation at a hydrophobic/hydrophilic interface, which enables destabilization of the membranes. In this paper, sequence analysis and molecular modelling predict that the 67-78 fragment of alpha-synuclein is a tilted peptide. Its destabilizing properties were tested experimentally. The alpha-synuclein 67-78 peptide is able to induce lipid mixing and leakage of unilamellar liposomes. The neuronal toxicity, studied using human neuroblastoma cells, demonstrated that the alpha-synuclein 67-78 peptide induces neurotoxicity. A mutant designed by molecular modelling to be amphipathic was shown to be significantly less fusogenic and toxic than the wild type. In conclusion, we have identified a tilted peptide in alpha-synuclein, which could be involved in the toxicity induced during amyloidogenesis of alpha-synuclein. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aca9fbb7c3a557f69e6031f8341c9b16 https://hal.archives-ouvertes.fr/hal-03513564 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....aca9fbb7c3a557f69e6031f8341c9b16 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |