Crystal structure of a highly conserved enteroviral 5' cloverleaf RNA replication element.

Autor: Das NK; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA., Hollmann NM; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.; Howard Hughes Medical Institute, University of Maryland Baltimore County, Baltimore, MD, 21250, USA., Vogt J; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA., Sevdalis SE; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Banna HA; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA., Ojha M; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA., Koirala D; Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD, 21250, USA. dkoirala@umbc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 07; Vol. 14 (1), pp. 1955. Date of Electronic Publication: 2023 Apr 07.
DOI: 10.1038/s41467-023-37658-8
Abstrakt: The extreme 5'-end of the enterovirus RNA genome contains a conserved cloverleaf-like domain that recruits 3CD and PCBP proteins required for initiating genome replication. Here, we report the crystal structure at 1.9 Å resolution of this domain from the CVB3 genome in complex with an antibody chaperone. The RNA folds into an antiparallel H-type four-way junction comprising four subdomains with co-axially stacked sA-sD and sB-sC helices. Long-range interactions between a conserved A40 in the sC-loop and Py-Py helix within the sD subdomain organize near-parallel orientations of the sA-sB and sC-sD helices. Our NMR studies confirm that these long-range interactions occur in solution and without the chaperone. The phylogenetic analyses indicate that our crystal structure represents a conserved architecture of enteroviral cloverleaf-like domains, including the A40 and Py-Py interactions. The protein binding studies further suggest that the H-shape architecture provides a ready-made platform to recruit 3CD and PCBP2 for viral replication.
(© 2023. The Author(s).)
Databáze: MEDLINE
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