Academic Journal
A 5+1 assemble-to-activate mechanism of the Lon proteolytic machine
| العنوان: | A 5+1 assemble-to-activate mechanism of the Lon proteolytic machine |
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| المؤلفون: | Li, Shanshan, Hsieh, Kan-Yen, Kuo, Chiao-I, Lin, Tzu-Chi, Lee, Szu-Hui, Chen, Yi-Ru, Wang, Chun-Hsiung, Ho, Meng-Ru, Ting, See-Yeun, Zhang, Kaiming, Chang, Chung-I |
| المساهمون: | Academia Sinica |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Many AAA+ (ATPases associated with diverse cellular activities) proteins function as protein or DNA remodelers by threading the substrate through the central pore of their hexameric assemblies. In this ATP-dependent translocating state, the substrate is gripped by the pore loops of the ATPase domains arranged in a universal right-handed spiral staircase organization. However, the process by which a AAA+ protein is activated to adopt this substrate-pore-loop arrangement remains unknown. We show here, using cryo-electron microscopy (cryo-EM), that the activation process of the Lon AAA+ protease may involve a pentameric assembly and a substrate-dependent incorporation of the sixth protomer to form the substrate-pore-loop contacts seen in the translocating state. Based on the structural results, we design truncated monomeric mutants that inhibit Lon activity by binding to the native pentamer and demonstrated that expressing these monomeric mutants in Escherichia coli cells containing functional Lon elicits specific phenotypes associated with lon deficiency, including the inhibition of persister cell formation. These findings uncover a substrate-dependent assembly process for the activation of a AAA+ protein and demonstrate a targeted approach to selectively inhibit its function within cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-43035-2 |
| الاتاحة: | http://dx.doi.org/10.1038/s41467-023-43035-2 https://www.nature.com/articles/s41467-023-43035-2.pdf https://www.nature.com/articles/s41467-023-43035-2 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.6273845 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-43035-2 |
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