Structural basis for RNA-duplex unwinding by the DEAD-box helicase DbpA.


Journal

RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184

Informations de publication

Date de publication:
09 2023
Historique:
received: 08 01 2023
accepted: 29 04 2023
medline: 18 8 2023
pubmed: 24 5 2023
entrez: 23 5 2023
Statut: ppublish

Résumé

DEAD-box RNA helicases are implicated in most aspects of RNA biology, where these enzymes unwind short RNA duplexes in an ATP-dependent manner. During the central step of the unwinding cycle, the two domains of the helicase core form a distinct closed conformation that destabilizes the RNA duplex, which ultimately leads to duplex melting. Despite the importance of this step for the unwinding process no high-resolution structures of this state are available. Here, I used nuclear magnetic resonance spectroscopy and X-ray crystallography to determine structures of the DEAD-box helicase DbpA in the closed conformation, complexed with substrate duplexes and single-stranded unwinding product. These structures reveal that DbpA initiates duplex unwinding by interacting with up to three base-paired nucleotides and a 5' single-stranded RNA duplex overhang. These high-resolution snapshots, together with biochemical assays, rationalize the destabilization of the RNA duplex and are integrated into a conclusive model of the unwinding process.

Identifiants

pubmed: 37221012
pii: rna.079582.123
doi: 10.1261/rna.079582.123
pmc: PMC10573307
doi:

Substances chimiques

Adenosine Triphosphate 8L70Q75FXE
DEAD-box RNA Helicases EC 3.6.4.13
DNA Helicases EC 3.6.4.-
RNA 63231-63-0
dbpA protein, E coli EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1339-1354

Informations de copyright

© 2023 Wurm; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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Auteurs

Jan Philip Wurm (JP)

Institute of Biophysics and Physical Biochemistry, Regensburg Center for Biochemistry, University of Regensburg, 93053 Regensburg, Germany jan-philip.wurm@ur.de.

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Classifications MeSH