Academic Journal
Molecular Dynamics Simulations Elucidate the Molecular Basis of Pre-mRNA Translocation by the Prp2 Spliceosomal Helicase
| العنوان: | Molecular Dynamics Simulations Elucidate the Molecular Basis of Pre-mRNA Translocation by the Prp2 Spliceosomal Helicase |
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| المؤلفون: | Agrò, Sefora Naomi, Rozza, Riccardo, Movilla Núñez, Santiago, Aupič, Jana, Magistrato, Alessandra |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2023 |
| المجموعة: | Repositori Universitat Jaume I (Repositorio UJI) |
| مصطلحات موضوعية: | spliceosome, pre-mRNA, helicase, 3. Salud y bienestar |
| الوصف: | The spliceosome machinery catalyzes precursor-messenger RNA (pre-mRNA) splicing by undergoing at each splicing cycle assembly, activation, catalysis, and disassembly processes, thanks to the concerted action of specific RNA-dependent ATPases/helicases. Prp2, a member of the DExH-box ATPase/helicase family, harnesses the energy of ATP hydrolysis to translocate a single pre-mRNA strand in the 5′ to 3′ direction, thus promoting spliceosome remodeling to its catalytic-competent state. Here, we established the functional coupling between ATPase and helicase activities of Prp2. Namely, extensive multi-μs molecular dynamics simulations allowed us to unlock how, after pre-mRNA selection, ATP binding, hydrolysis, and dissociation induce a functional typewriter-like rotation of the Prp2 C-terminal domain. This movement, endorsed by an iterative swing of interactions established between specific Prp2 residues with the nucleobases at 5′- and 3′-ends of pre-mRNA, promotes pre-mRNA translocation. Notably, some of these Prp2 residues are conserved in the DExH-box family, suggesting that the translocation mechanism elucidated here may be applicable to all DExH-box helicases. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 10 p.; application/pdf |
| اللغة: | English |
| Relation: | https://doi.org/10.1021/acs.jcim.3c00585; http://hdl.handle.net/10234/204707 |
| DOI: | 10.1021/acs.jcim.3c00585 |
| الاتاحة: | http://hdl.handle.net/10234/204707 https://doi.org/10.1021/acs.jcim.3c00585 |
| Rights: | Copyright © 2023 American Chemical Society ; info:eu-repo/semantics/restrictedAccess ; http://rightsstatements.org/vocab/InC/1.0/ |
| رقم الانضمام: | edsbas.9A2E7470 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jcim.3c00585 |
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