SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease

Bibliographic Details
Main Author: Salgueiro, Bruno A.
Publication Date: 2024
Other Authors: Saramago, Margarida, Tully, Mark D., Issoglio, Federico, Silva, Sara T.N., Paiva, Ana C.F., Arraiano, Cecília M., Matias, Pedro M., Matos, Rute G., Moe, Elin, Romão, Célia V.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/182879
Summary: Funding Information: Open access funding provided by FCT|FCCN (b-on). This study was financially supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT), Project MOSTMICRO-ITQB with references UIDB/04612/2020 and UIDP/04612/2020, iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and LS4FUTURE Associated Laboratory (LA/P/0087/2020). BAS is recipient of FCT PhD4COVID grant SFRH/BD/08066/2020; RGM is a recipient of an FCT CEEC contract (CEECIND/02065/2017); MS and EM are recipients of FCT DL57; CVR is recipient of FCT Institutional CEEC. Publisher Copyright: © The Author(s) 2024.
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spelling SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonucleaseBiophysicsCoronavirusMagnesiumManganeseNucleaseSAXSBiomaterialsBiochemistry, Genetics and Molecular Biology(all)Agricultural and Biological Sciences(all)Metals and AlloysFunding Information: Open access funding provided by FCT|FCCN (b-on). This study was financially supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT), Project MOSTMICRO-ITQB with references UIDB/04612/2020 and UIDP/04612/2020, iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and LS4FUTURE Associated Laboratory (LA/P/0087/2020). BAS is recipient of FCT PhD4COVID grant SFRH/BD/08066/2020; RGM is a recipient of an FCT CEEC contract (CEECIND/02065/2017); MS and EM are recipients of FCT DL57; CVR is recipient of FCT Institutional CEEC. Publisher Copyright: © The Author(s) 2024.Over recent years, we have been living under a pandemic, caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). One of the major virulence factors of Coronaviruses is the Non-structural protein 1 (Nsp1), known to suppress the host cells protein translation machinery, allowing the virus to produce its own proteins, propagate and invade new cells. To unveil the molecular mechanisms of SARS-CoV2 Nsp1, we have addressed its biochemical and biophysical properties in the presence of calcium, magnesium and manganese. Our findings indicate that the protein in solution is a monomer and binds to both manganese and calcium, with high affinity. Surprisingly, our results show that SARS-CoV2 Nsp1 alone displays metal-dependent endonucleolytic activity towards both RNA and DNA, regardless of the presence of host ribosome. These results show Nsp1 as new nuclease within the coronavirus family. Furthermore, the Nsp1 double variant R124A/K125A presents no nuclease activity for RNA, although it retains activity for DNA, suggesting distinct binding sites for DNA and RNA. Thus, we present for the first time, evidence that the activities of Nsp1 are modulated by the presence of different metals, which are proposed to play an important role during viral infection. This research contributes significantly to our understanding of the mechanisms of action of Coronaviruses.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNSalgueiro, Bruno A.Saramago, MargaridaTully, Mark D.Issoglio, FedericoSilva, Sara T.N.Paiva, Ana C.F.Arraiano, Cecília M.Matias, Pedro M.Matos, Rute G.Moe, ElinRomão, Célia V.2025-05-08T21:30:07Z2024-03-282024-03-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/182879eng0966-0844PURE: 90628418https://doi.org/10.1007/s10534-024-00596-zinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-05-19T01:40:15Zoai:run.unl.pt:10362/182879Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T07:14:13.344949Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
title SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
spellingShingle SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
Salgueiro, Bruno A.
Biophysics
Coronavirus
Magnesium
Manganese
Nuclease
SAXS
Biomaterials
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Metals and Alloys
title_short SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
title_full SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
title_fullStr SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
title_full_unstemmed SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
title_sort SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease
author Salgueiro, Bruno A.
author_facet Salgueiro, Bruno A.
Saramago, Margarida
Tully, Mark D.
Issoglio, Federico
Silva, Sara T.N.
Paiva, Ana C.F.
Arraiano, Cecília M.
Matias, Pedro M.
Matos, Rute G.
Moe, Elin
Romão, Célia V.
author_role author
author2 Saramago, Margarida
Tully, Mark D.
Issoglio, Federico
Silva, Sara T.N.
Paiva, Ana C.F.
Arraiano, Cecília M.
Matias, Pedro M.
Matos, Rute G.
Moe, Elin
Romão, Célia V.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Salgueiro, Bruno A.
Saramago, Margarida
Tully, Mark D.
Issoglio, Federico
Silva, Sara T.N.
Paiva, Ana C.F.
Arraiano, Cecília M.
Matias, Pedro M.
Matos, Rute G.
Moe, Elin
Romão, Célia V.
dc.subject.por.fl_str_mv Biophysics
Coronavirus
Magnesium
Manganese
Nuclease
SAXS
Biomaterials
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Metals and Alloys
topic Biophysics
Coronavirus
Magnesium
Manganese
Nuclease
SAXS
Biomaterials
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Metals and Alloys
description Funding Information: Open access funding provided by FCT|FCCN (b-on). This study was financially supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT), Project MOSTMICRO-ITQB with references UIDB/04612/2020 and UIDP/04612/2020, iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and LS4FUTURE Associated Laboratory (LA/P/0087/2020). BAS is recipient of FCT PhD4COVID grant SFRH/BD/08066/2020; RGM is a recipient of an FCT CEEC contract (CEECIND/02065/2017); MS and EM are recipients of FCT DL57; CVR is recipient of FCT Institutional CEEC. Publisher Copyright: © The Author(s) 2024.
publishDate 2024
dc.date.none.fl_str_mv 2024-03-28
2024-03-28T00:00:00Z
2025-05-08T21:30:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/182879
url http://hdl.handle.net/10362/182879
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0966-0844
PURE: 90628418
https://doi.org/10.1007/s10534-024-00596-z
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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