The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X
Abstract
DEAD-box helicases (DDXs) regulate RNA processing and metabolism by unwinding short double-stranded (ds) RNAs. Sharing a helicase core composed of two RecA-like domains (D1D2), DDXs function in an ATP-dependent, non-processive manner. As an attractive target for cancer and AIDS treatment, DDX3X and its orthologs are extensively studied, yielding a wealth of biochemical and biophysical data, including structures of apo-D1D2 and post-unwound D1D2:single-stranded RNA complex, and the structure of a D2:dsRNA complex that is thought to represent a pre-unwound state. However, the structure of a pre-unwound D1D2:dsRNA complex remains elusive, and thus, the mechanism of DDX action is not fully understood. Here, we describe the structure of a D1D2 core in complex with a 23-base pair dsRNA at pre-unwound state, revealing that two DDXs recognize a 2-turn dsRNA, each DDX mainly recognizes a single RNA strand, and conformational changes induced by ATP binding unwinds the RNA duplex in a cooperative manner.
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH); National Cancer Institute (NCI); Center for Cancer Research
- OSTI Identifier:
- 1557302
- Grant/Contract Number:
- AC02-06CH11357; 22978
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; enzyme mechanisms; RNA metabolism; SAXS; x-ray crystallography
Citation Formats
Song, He, and Ji, Xinhua. The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X. United States: N. p., 2019.
Web. doi:10.1038/s41467-019-11083-2.
Song, He, & Ji, Xinhua. The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X. United States. https://doi.org/10.1038/s41467-019-11083-2
Song, He, and Ji, Xinhua. Fri .
"The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X". United States. https://doi.org/10.1038/s41467-019-11083-2. https://www.osti.gov/servlets/purl/1557302.
@article{osti_1557302,
title = {The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X},
author = {Song, He and Ji, Xinhua},
abstractNote = {DEAD-box helicases (DDXs) regulate RNA processing and metabolism by unwinding short double-stranded (ds) RNAs. Sharing a helicase core composed of two RecA-like domains (D1D2), DDXs function in an ATP-dependent, non-processive manner. As an attractive target for cancer and AIDS treatment, DDX3X and its orthologs are extensively studied, yielding a wealth of biochemical and biophysical data, including structures of apo-D1D2 and post-unwound D1D2:single-stranded RNA complex, and the structure of a D2:dsRNA complex that is thought to represent a pre-unwound state. However, the structure of a pre-unwound D1D2:dsRNA complex remains elusive, and thus, the mechanism of DDX action is not fully understood. Here, we describe the structure of a D1D2 core in complex with a 23-base pair dsRNA at pre-unwound state, revealing that two DDXs recognize a 2-turn dsRNA, each DDX mainly recognizes a single RNA strand, and conformational changes induced by ATP binding unwinds the RNA duplex in a cooperative manner.},
doi = {10.1038/s41467-019-11083-2},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {Fri Jul 12 00:00:00 EDT 2019},
month = {Fri Jul 12 00:00:00 EDT 2019}
}
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Works referencing / citing this record:
DDX3X Multifunctionally Modulates Tumor Progression and Serves as a Prognostic Indicator to Predict Cancer Outcomes
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