دورية أكاديمية
Filamentation modulates allosteric regulation of PRPS
| العنوان: | Filamentation modulates allosteric regulation of PRPS |
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| المؤلفون: | Huan-Huan Hu, Guang-Ming Lu, Chia-Chun Chang, Yilan Li, Jiale Zhong, Chen-Jun Guo, Xian Zhou, Boqi Yin, Tianyi Zhang, Ji-Long Liu |
| المصدر: | eLife, Vol 11 (2022) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | PRPS, cytoophidium, allosteric regulation, Cryo-EM, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Phosphoribosyl pyrophosphate (PRPP) is a key intermediate in the biosynthesis of purine and pyrimidine nucleotides, histidine, tryptophan, and cofactors NAD and NADP. Abnormal regulation of PRPP synthase (PRPS) is associated with human disorders, including Arts syndrome, retinal dystrophy, and gouty arthritis. Recent studies have demonstrated that PRPS can form filamentous cytoophidia in eukaryotes. Here, we show that PRPS forms cytoophidia in prokaryotes both in vitro and in vivo. Moreover, we solve two distinct filament structures of E. coli PRPS at near-atomic resolution using Cryo-EM. The formation of the two types of filaments is controlled by the binding of different ligands. One filament type is resistant to allosteric inhibition. The structural comparison reveals conformational changes of a regulatory flexible loop, which may regulate the binding of the allosteric inhibitor and the substrate ATP. A noncanonical allosteric AMP/ADP binding site is identified to stabilize the conformation of the regulatory flexible loop. Our findings not only explore a new mechanism of PRPS regulation with structural basis, but also propose an additional layer of cell metabolism through PRPS filamentation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/79552; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.79552 |
| URL الوصول: | https://doaj.org/article/46c77353daa547c5963b470113dda424 |
| رقم الأكسشن: | edsdoj.46c77353daa547c5963b470113dda424 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.79552 |