التفاصيل البيبلوغرافية
| العنوان: |
Copper drives prion protein phase separation and modulates aggregation |
| المؤلفون: |
do Amaral, Mariana Juliani, Mohapatra, Satabdee, Passos, Aline Ribeiro, Lopes da Silva, Taiana Sousa, Carvalho, Renato Sampaio, da Silva Almeida, Marcius, Pinheiro, Anderson Sá, Wegmann, Susanne, Cordeiro, Yraima |
| المصدر: |
Science Advances ; volume 9, issue 44 ; ISSN 2375-2548 |
| بيانات النشر: |
American Association for the Advancement of Science (AAAS) |
| سنة النشر: |
2023 |
| الوصف: |
Prion diseases are characterized by prion protein (PrP) transmissible aggregation and neurodegeneration, which has been linked to oxidative stress. The physiological function of PrP seems related to sequestering of redox-active Cu 2+ , and Cu 2+ dyshomeostasis is observed in prion disease brain. It is unclear whether Cu 2+ contributes to PrP aggregation, recently shown to be mediated by PrP condensation. This study indicates that Cu 2+ promotes PrP condensation in live cells at the cell surface and in vitro through copartitioning. Molecularly, Cu 2+ inhibited PrP β-structure and hydrophobic residues exposure. Oxidation, induced by H 2 O 2 , triggered liquid-to-solid transition of PrP:Cu 2+ condensates and promoted amyloid-like PrP aggregation. In cells, overexpression of PrP C initially protected against Cu 2+ cytotoxicity but led to PrP C aggregation upon extended copper exposure. Our data suggest that PrP condensates function as a buffer for copper that prevents copper toxicity but can transition into PrP aggregation at prolonged oxidative stress. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1126/sciadv.adi7347 |
| الإتاحة: |
https://doi.org/10.1126/sciadv.adi7347Test |
| رقم الانضمام: |
edsbas.FE8C3F4A |
| قاعدة البيانات: |
BASE |
