دورية أكاديمية
Aggregation pathways of human γ D crystallin induced by metal ions revealed by time dependent methods
| العنوان: | Aggregation pathways of human γ D crystallin induced by metal ions revealed by time dependent methods |
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| المؤلفون: | Arline Fernández-Silva, Leidys French-Pacheco, Lina Rivillas-Acevedo, Carlos Amero |
| المصدر: | PeerJ, Vol 8, p e9178 (2020) |
| بيانات النشر: | PeerJ Inc., 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Biology (General) |
| مصطلحات موضوعية: | Crystallins, Copper, Zinc, Cataracts, Aggregation, Real-time NMR, Medicine, Biology (General), QH301-705.5 |
| الوصف: | Cataract formation is a slow accumulative process due to protein aggregates promoted by different factors over time. Zinc and copper ions have been reported to induce the formation of aggregates opaque to light in the human gamma D crystallin (HγD) in a concentration and temperature dependent manner. In order to gain insight into the mechanism of metal-induced aggregation of HγD under conditions that mimic more closely the slow, accumulative process of the disease, we have studied the non-equilibrium process with the minimal metal dose that triggers HγD aggregation. Using a wide variety of biophysics techniques such as turbidimetry, dynamic light scattering, fluorescence, nuclear magnetic resonance and computational methods, we obtained information on the molecular mechanisms for the formation of aggregates. Zn(II) ions bind to different regions at the protein, probably with similar affinities. This binding induces a small conformational rearrangement within and between domains and aggregates via the formation of metal bridges without any detectable unfolded intermediates. In contrast, Cu(II)-induced aggregation includes a lag time, in which the N-terminal domain partially unfolds while the C-terminal domain and parts of the N-terminal domain remain in a native-like conformation. This partially unfolded intermediate is prone to form the high-molecular weight aggregates. Our results clearly show that different external factors can promote protein aggregation following different pathways. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2167-8359 |
| العلاقة: | https://peerj.com/articles/9178.pdfTest; https://peerj.com/articles/9178Test/; https://doaj.org/toc/2167-8359Test |
| DOI: | 10.7717/peerj.9178 |
| الوصول الحر: | https://doaj.org/article/2885bb62f4be45c48dd4c9803649e2edTest |
| رقم الانضمام: | edsdoj.2885bb62f4be45c48dd4c9803649e2ed |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21678359 |
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| DOI: | 10.7717/peerj.9178 |