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    Comparative structural and functional analysis of Bunyavirus and Arenavirus cap-snatching Endonucleases

    Rey, F.A. and Reguera, J. and Gerlach, P. and Rosenthal, M. and Gaudon, S. and Coscia, Francesca and Günther, S. and Cusack, S. (2016) Comparative structural and functional analysis of Bunyavirus and Arenavirus cap-snatching Endonucleases. PLOS Pathogens 12 (6), e1005636. ISSN 1553-7374.

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    Abstract

    Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5′ end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 05 Aug 2016 08:50
    Last Modified: 06 Oct 2016 08:18
    URI: http://eprints.bbk.ac.uk/id/eprint/15840

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