Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Structure and function of the Toscana virus cap-snatching endonuclease

Abstract : Toscana virus (TOSV) is an arthropod-borne human pathogen responsible for seasonal outbreaks of fever and meningoencephalitis in the Mediterranean basin. TOSV is a segmented negative-strand RNA virus (sNSV) that belongs to the genus phlebovirus (family Phenuiviridae, order Bunyavirales), encompassing other important human pathogens such as Rift Valley fever virus (RVFV). Here, we carried out a structural and functional characterization of the TOSV cap-snatching endonuclease, an N terminal domain of the viral polymerase (L protein) that provides capped 3 OH primers for transcription. We report TOSV endonuclease crystal structures in the apo form, in complex with a di-ketoacid inhibitor (DPBA) and in an intermediate state of inhibitor release , showing details on substrate binding and active site dynamics. The structure reveals substantial folding rearrangements absent in previously reported cap-snatching endonucleases. These include the relocation of the N terminus and the appearance of new structural motifs important for transcription and replication. The enzyme shows high activity rates comparable to other His+ cap-snatching en-donucleases. Moreover, the activity is dependent on conserved residues involved in metal ion and sub-strate binding. Altogether, these results bring new light on the structure and function of cap-snatching endonucleases and pave the way for the development of specific and broad-spectrum antivirals.
Document type :
Journal articles
Complete list of metadata

Cited literature [52 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-02611184
Contributor : Julien Caugant Connect in order to contact the contributor
Submitted on : Monday, May 18, 2020 - 11:25:35 AM
Last modification on : Thursday, March 3, 2022 - 3:24:03 PM

File

gkz838.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License

Identifiers

Collections

Citation

Rhian Jones, Sana Lessoued, Kristina Meier, Stéphanie Devignot, Sergio Barata-García, et al.. Structure and function of the Toscana virus cap-snatching endonuclease. Nucleic Acids Research, Oxford University Press, 2019, 47, pp.10914-10930. ⟨10.1093/nar/gkz838⟩. ⟨hal-02611184⟩

Share

Metrics

Record views

200

Files downloads

242