NMR characterization of RNA binding property of the DEAD-box RNA helicase DDX3X and its implications for helicase activity.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 Apr 2024
25 Apr 2024
Historique:
received:
17
10
2023
accepted:
05
04
2024
medline:
26
4
2024
pubmed:
26
4
2024
entrez:
25
4
2024
Statut:
epublish
Résumé
The DEAD-box RNA helicase (DDX) plays a central role in many aspects of RNA metabolism by remodeling the defined structure of RNA molecules. While a number of structural studies have revealed the atomistic details of the interaction between DDX and RNA ligands, the molecular mechanism of how this molecule unwinds a structured RNA into an unstructured single-stranded RNA (ssRNA) has largely remained elusive. This is due to challenges in structurally characterizing the unwinding intermediate state and the lack of thermodynamic details underlying this process. In this study, we use solution nuclear magnetic resonance (NMR) spectroscopy to characterize the interaction of human DDX3X, a member of the DDX family, with various RNA ligands. Our results show that the inherent binding affinity of DDX3X for ssRNA is significantly higher than that for structured RNA elements. This preferential binding, accompanied by the formation of a domain-closed conformation in complex with ssRNA, effectively stabilizes the denatured ssRNA state and thus underlies the unwinding activity of DDX3X. Our results provide a thermodynamic and structural basis for the DDX function, whereby DDX can recognize and remodel a distinct set of structured RNAs to participate in a wide range of physiological processes.
Identifiants
pubmed: 38664397
doi: 10.1038/s41467-024-47659-w
pii: 10.1038/s41467-024-47659-w
doi:
Substances chimiques
DEAD-box RNA Helicases
EC 3.6.4.13
DDX3X protein, human
EC 3.6.1.-
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3303Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21ae0121028
Informations de copyright
© 2024. The Author(s).
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