دورية أكاديمية
Binding structures of SERF1a with NT17-polyQ peptides of huntingtin exon 1 revealed by SEC-SWAXS, NMR and molecular simulation
| العنوان: | Binding structures of SERF1a with NT17-polyQ peptides of huntingtin exon 1 revealed by SEC-SWAXS, NMR and molecular simulation |
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| المؤلفون: | Tien-Chang Lin, Orion Shih, Tien-Ying Tsai, Yi-Qi Yeh, Kuei-Fen Liao, Bradley W. Mansel, Ying-Jen Shiu, Chi-Fon Chang, An-Chung Su, Yun-Ru Chen, U-Ser Jeng |
| المصدر: | IUCrJ, Vol 11, Iss 5, Pp 849-858 (2024) |
| بيانات النشر: | International Union of Crystallography, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Crystallography |
| مصطلحات موضوعية: | huntingtin exon 1, polyglutamine peptides, serf1a, sec-swaxs, nmr, molecular simulation, huntington's disease, Crystallography, QD901-999 |
| الوصف: | The aberrant fibrillization of huntingtin exon 1 (Httex1) characterized by an expanded polyglutamine (polyQ) tract is a defining feature of Huntington's disease, a neurodegenerative disorder. Recent investigations underscore the involvement of a small EDRK-rich factor 1a (SERF1a) in promoting Httex1 fibrillization through interactions with its N terminus. By establishing an integrated approach with size-exclusion-column-based small- and wide-angle X-ray scattering (SEC-SWAXS), NMR, and molecular simulations using Rosetta, the analysis here reveals a tight binding of two NT17 fragments of Httex1 (comprising the initial 17 amino acids at the N terminus) to the N-terminal region of SERF1a. In contrast, examination of the complex structure of SERF1a with a coiled NT17-polyQ peptide (33 amino acids in total) indicates sparse contacts of the NT17 and polyQ segments with the N-terminal side of SERF1a. Furthermore, the integrated SEC-SWAXS and molecular-simulation analysis suggests that the coiled NT17 segment can transform into a helical conformation when associated with a polyQ segment exhibiting high helical content. Intriguingly, NT17-polyQ peptides with enhanced secondary structures display diminished interactions with SERF1a. This insight into the conformation-dependent binding of NT17 provides clues to a catalytic association mechanism underlying SERF1a's facilitation of Httext1 fibrillization. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2052-2525 20522525 |
| Relation: | https://journals.iucr.org/paper?S2052252524006341; https://doaj.org/toc/2052-2525 |
| DOI: | 10.1107/S2052252524006341 |
| URL الوصول: | https://doaj.org/article/209dc44d9cfb417082cdde097083b7a8 |
| رقم الأكسشن: | edsdoj.209dc44d9cfb417082cdde097083b7a8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20522525 |
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| DOI: | 10.1107/S2052252524006341 |