Please use this identifier to cite or link to this item:
doi:10.22028/D291-39710
Title: | Continuous millisecond conformational cycle of a DEAH box helicase reveals control of domain motions by atomic-scale transitions |
Author(s): | Becker, Robert A. Hub, Jochen S. |
Language: | English |
Title: | Communications Biology |
Volume: | 6 |
Issue: | 1 |
Publisher/Platform: | Springer Nature |
Year of Publication: | 2023 |
Free key words: | Computational biology and bioinformatics Computational biophysics Molecular conformation RNA splicing |
DDC notations: | 500 Science |
Publikation type: | Journal Article |
Abstract: | Helicases are motor enzymes found in every living organism and viruses, where they maintain the stability of the genome and control against false recombination. The DEAH-box helicase Prp43 plays a crucial role in pre-mRNA splicing in unicellular organisms by translocating single-stranded RNA. The molecular mechanisms and conformational transitions of helicases are not understood at the atomic level. We present a complete conformational cycle of RNA translocation by Prp43 in atomic detail based on molecular dynamics simulations. To enable the sampling of such complex transition on the millisecond timescale, we combined two enhanced sampling techniques, namely simulated tempering and adaptive sampling guided by crystallographic data. During RNA translocation, the center-of-mass motions of the RecAlike domains followed the established inchworm model, whereas the domains crawled along the RNA in a caterpillar-like movement, suggesting an inchworm/caterpillar model. However, this crawling required a complex sequence of atomic-scale transitions involving the release of an arginine finger from the ATP pocket, stepping of the hook-loop and hook-turn motifs along the RNA backbone, and several others. These findings highlight that large-scale domain dynamics may be controlled by complex sequences of atomic-scale transitions. |
DOI of the first publication: | 10.1038/s42003-023-04751-z |
URL of the first publication: | https://www.nature.com/articles/s42003-023-04751-z |
Link to this record: | urn:nbn:de:bsz:291--ds-397109 hdl:20.500.11880/35779 http://dx.doi.org/10.22028/D291-39710 |
ISSN: | 2399-3642 |
Date of registration: | 9-May-2023 |
Description of the related object: | Supplementary information |
Related object: | https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM2_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM3_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM4_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM5_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM6_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM7_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs42003-023-04751-z/MediaObjects/42003_2023_4751_MOESM8_ESM.pdf |
Faculty: | NT - Naturwissenschaftlich- Technische Fakultät |
Department: | NT - Physik |
Professorship: | NT - Prof. Dr. Jochen Hub |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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s42003-023-04751-z.pdf | 5,77 MB | Adobe PDF | View/Open |
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