دورية أكاديمية
Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate
| العنوان: | Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate |
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| المؤلفون: | Diana C Rodriguez Camargo, Kyle J Korshavn, Alexander Jussupow, Kolio Raltchev, David Goricanec, Markus Fleisch, Riddhiman Sarkar, Kai Xue, Michaela Aichler, Gabriele Mettenleiter, Axel Karl Walch, Carlo Camilloni, Franz Hagn, Bernd Reif, Ayyalusamy Ramamoorthy |
| المصدر: | eLife, Vol 6 (2017) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | membrane, Amyloid peptide, Structure, NMR, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique β-strand structure distinct from the conventional amyloid β-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/31226Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.31226 |
| الوصول الحر: | https://doaj.org/article/83e9a3672fef478bbca4e26152d644a1Test |
| رقم الانضمام: | edsdoj.83e9a3672fef478bbca4e26152d644a1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.31226 |