Structure and function of the Toscana virus cap-snatching endonuclease
International audience 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 Bun...
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ftanrparis:oai:HAL:hal-02611184v1 2024-09-15T17:51:35+00:00 Structure and function of the Toscana virus cap-snatching endonuclease Jones, Rhian Lessoued, Sana Meier, Kristina Devignot, Stéphanie Barata-García, Sergio Mate, Maria Bragagnolo, Gabriel Weber, Friedemann Rosenthal, Maria Reguera, Juan Architecture et fonction des macromolécules biologiques (AFMB) Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin Hamburg, Germany (BNITM) Justus-Liebig-Universität Gießen = Justus Liebig University (JLU) Fondation pour la Recherche Medicale DCM20181039531Fondation Bettencourt Schueller AGDI-531281German Research Foundation (DFG) 197785619 SFB 1021Leibniz competition programme K72/2017Fondation pour la Recherche Medical chimiepour la medecine DCM20181039531 ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010) European Project: 9732732(1998) 2019 https://amu.hal.science/hal-02611184 https://amu.hal.science/hal-02611184/document https://amu.hal.science/hal-02611184/file/gkz838.pdf https://doi.org/10.1093/nar/gkz838 en eng HAL CCSD Oxford University Press info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkz838 info:eu-repo/semantics/altIdentifier/pmid/31584100 info:eu-repo/grantAgreement//9732732/EU/Collaborative Research: Winter C Flux in Arctic Ecosystems Under Changing Climate: Effects of Soil Carbon and Active Layer Dynamics/ hal-02611184 https://amu.hal.science/hal-02611184 https://amu.hal.science/hal-02611184/document https://amu.hal.science/hal-02611184/file/gkz838.pdf doi:10.1093/nar/gkz838 PUBMED: 31584100 WOS: 000501735500042 http://creativecommons.org/licenses/by-nc/ info:eu-repo/semantics/OpenAccess ISSN: 0305-1048 EISSN: 1362-4962 Nucleic Acids Research https://amu.hal.science/hal-02611184 Nucleic Acids Research, 2019, 47, pp.10914-10930. ⟨10.1093/nar/gkz838⟩ [SDV]Life Sciences [q-bio] info:eu-repo/semantics/article Journal articles 2019 ftanrparis https://doi.org/10.1093/nar/gkz838 2024-07-12T11:16:27Z International audience 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. Article in Journal/Newspaper Arctic Portail HAL-ANR (Agence Nationale de la Recherche) Nucleic Acids Research 47 20 10914 10930 |
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Portail HAL-ANR (Agence Nationale de la Recherche) |
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[SDV]Life Sciences [q-bio] |
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[SDV]Life Sciences [q-bio] Jones, Rhian Lessoued, Sana Meier, Kristina Devignot, Stéphanie Barata-García, Sergio Mate, Maria Bragagnolo, Gabriel Weber, Friedemann Rosenthal, Maria Reguera, Juan Structure and function of the Toscana virus cap-snatching endonuclease |
topic_facet |
[SDV]Life Sciences [q-bio] |
description |
International audience 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. |
author2 |
Architecture et fonction des macromolécules biologiques (AFMB) Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin Hamburg, Germany (BNITM) Justus-Liebig-Universität Gießen = Justus Liebig University (JLU) Fondation pour la Recherche Medicale DCM20181039531Fondation Bettencourt Schueller AGDI-531281German Research Foundation (DFG) 197785619 SFB 1021Leibniz competition programme K72/2017Fondation pour la Recherche Medical chimiepour la medecine DCM20181039531 ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010) European Project: 9732732(1998) |
format |
Article in Journal/Newspaper |
author |
Jones, Rhian Lessoued, Sana Meier, Kristina Devignot, Stéphanie Barata-García, Sergio Mate, Maria Bragagnolo, Gabriel Weber, Friedemann Rosenthal, Maria Reguera, Juan |
author_facet |
Jones, Rhian Lessoued, Sana Meier, Kristina Devignot, Stéphanie Barata-García, Sergio Mate, Maria Bragagnolo, Gabriel Weber, Friedemann Rosenthal, Maria Reguera, Juan |
author_sort |
Jones, Rhian |
title |
Structure and function of the Toscana virus cap-snatching endonuclease |
title_short |
Structure and function of the Toscana virus cap-snatching endonuclease |
title_full |
Structure and function of the Toscana virus cap-snatching endonuclease |
title_fullStr |
Structure and function of the Toscana virus cap-snatching endonuclease |
title_full_unstemmed |
Structure and function of the Toscana virus cap-snatching endonuclease |
title_sort |
structure and function of the toscana virus cap-snatching endonuclease |
publisher |
HAL CCSD |
publishDate |
2019 |
url |
https://amu.hal.science/hal-02611184 https://amu.hal.science/hal-02611184/document https://amu.hal.science/hal-02611184/file/gkz838.pdf https://doi.org/10.1093/nar/gkz838 |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
ISSN: 0305-1048 EISSN: 1362-4962 Nucleic Acids Research https://amu.hal.science/hal-02611184 Nucleic Acids Research, 2019, 47, pp.10914-10930. ⟨10.1093/nar/gkz838⟩ |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkz838 info:eu-repo/semantics/altIdentifier/pmid/31584100 info:eu-repo/grantAgreement//9732732/EU/Collaborative Research: Winter C Flux in Arctic Ecosystems Under Changing Climate: Effects of Soil Carbon and Active Layer Dynamics/ hal-02611184 https://amu.hal.science/hal-02611184 https://amu.hal.science/hal-02611184/document https://amu.hal.science/hal-02611184/file/gkz838.pdf doi:10.1093/nar/gkz838 PUBMED: 31584100 WOS: 000501735500042 |
op_rights |
http://creativecommons.org/licenses/by-nc/ info:eu-repo/semantics/OpenAccess |
op_doi |
https://doi.org/10.1093/nar/gkz838 |
container_title |
Nucleic Acids Research |
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47 |
container_issue |
20 |
container_start_page |
10914 |
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10930 |
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1810293531879669760 |