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

Author

Listed:
  • Naba K. Das

    (University of Maryland Baltimore County)

  • Nele M. Hollmann

    (University of Maryland Baltimore County
    University of Maryland Baltimore County)

  • Jeff Vogt

    (University of Maryland Baltimore County)

  • Spiridon E. Sevdalis

    (University of Maryland School of Medicine)

  • Hasan A. Banna

    (University of Maryland Baltimore County)

  • Manju Ojha

    (University of Maryland Baltimore County)

  • Deepak Koirala

    (University of Maryland Baltimore County)

Abstract

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.

Suggested Citation

  • Naba K. Das & Nele M. Hollmann & Jeff Vogt & Spiridon E. Sevdalis & Hasan A. Banna & Manju Ojha & Deepak Koirala, 2023. "Crystal structure of a highly conserved enteroviral 5′ cloverleaf RNA replication element," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37658-8
    DOI: 10.1038/s41467-023-37658-8
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    1. Shaileja Chopra & Andrés Palencia & Cornelia Virus & Sarah Schulwitz & Brenda R. Temple & Stephen Cusack & John Reader, 2016. "Structural characterization of antibiotic self-immunity tRNA synthetase in plant tumour biocontrol agent," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
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