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

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 chape...

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Published inNature communications Vol. 14; no. 1; p. 1955
Main Authors Das, Naba K., Hollmann, Nele M., Vogt, Jeff, Sevdalis, Spiridon E., Banna, Hasan A., Ojha, Manju, Koirala, Deepak
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.04.2023
Nature Publishing Group
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Summary: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. A cloverleaf-like RNA domain within the enterovirus genome is essential for replication. Here, the authors determine the 1.9 Å resolution crystal structure of such RNA from coxsackievirus B3 – a model enterovirus to study many other human viruses.
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content type line 23
AC02-06CH11357
USDOE
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-37658-8