Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role

To overcome their limited genetic capacity, numerous viruses encode multifunctional proteins. The birnavirus VP3 protein plays key roles during infection, including scaffolding of the viral capsid during morphogenesis, recruitment, and regulation of the viral RNA polymerase, shielding of the double-...

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Autores: Ferrero, Diego, Giménez. María Cecilia, Sagar, Amin, Rodríguez, Javier M., Castón, José R., Terebiznik, Mauricio R., Bernadó, Pau, Verdaguer, Núria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/379564
Acceso en línea:http://hdl.handle.net/10261/379564
Access Level:acceso abierto
Palabra clave:IBDV
dsRNA-binding protein
Moonlighting proteins
Scaffolding protein
Viral replication
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repository_id_str
dc.title.none.fl_str_mv Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
title Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
spellingShingle Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
Ferrero, Diego
IBDV
dsRNA-binding protein
Moonlighting proteins
Scaffolding protein
Viral replication
title_short Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
title_full Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
title_fullStr Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
title_full_unstemmed Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
title_sort Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical role
dc.creator.none.fl_str_mv Ferrero, Diego
Giménez. María Cecilia
Sagar, Amin
Rodríguez, Javier M.
Castón, José R.
Terebiznik, Mauricio R.
Bernadó, Pau
Verdaguer, Núria
author Ferrero, Diego
author_facet Ferrero, Diego
Giménez. María Cecilia
Sagar, Amin
Rodríguez, Javier M.
Castón, José R.
Terebiznik, Mauricio R.
Bernadó, Pau
Verdaguer, Núria
author_role author
author2 Giménez. María Cecilia
Sagar, Amin
Rodríguez, Javier M.
Castón, José R.
Terebiznik, Mauricio R.
Bernadó, Pau
Verdaguer, Núria
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Agence Nationale de la Recherche (France)
Comunidad de Madrid
Natural Sciences and Engineering Research Council of Canada
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv IBDV
dsRNA-binding protein
Moonlighting proteins
Scaffolding protein
Viral replication
topic IBDV
dsRNA-binding protein
Moonlighting proteins
Scaffolding protein
Viral replication
description To overcome their limited genetic capacity, numerous viruses encode multifunctional proteins. The birnavirus VP3 protein plays key roles during infection, including scaffolding of the viral capsid during morphogenesis, recruitment, and regulation of the viral RNA polymerase, shielding of the double-stranded RNA genome and targeting of host endosomes for genome replication, and immune evasion. The dimeric form of VP3 is critical for these functions. In previous work, we determined the X-ray structure of the central domains (D2–D3) of VP3 from the infectious bursal disease virus (IBDV). However, the structure and function of the IBDV VP3 N-terminal domain (D1) could not be determined at that time. Using integrated structural biology approaches and functional cell assays, here we characterize the IBDV VP3 D1 domain, unveiling its unexplored roles in virion stability and infection. The X-ray structure of D1 shows that this domain folds in four α-helices arranged in parallel dimers, which are essential for maintaining the dimeric arrangement of the full-length protein. Combining small-angle X-ray scattering analyses with molecular dynamics simulations allowed us to build a structural model for the D1–D3 domains. This model consists of an elongated structure with high flexibility in the D2–D3 connection, keeping D1 as the only driver of VP3 dimerization. Using reverse genetics tools, we show that the obliteration of D1 domain prevents the VP3 scaffold function during capsid assembly and severely impacts IBDV infection. Altogether, our study elucidates the structure of the VP3 D1 domain and reveals its role in VP3 protein dimerization and IBDV infection.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/379564
url http://hdl.handle.net/10261/379564
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117976GB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113287RB-I00
S2018/NMT-4389/NANOBIOCARGO-CM
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/pnasnexus/pgae521
https://doi.org/10.1093/pnasnexus/pgae521
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
National Academy of Sciences (U.S.)
publisher.none.fl_str_mv Oxford University Press
National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Structure of the aminoterminal domain of the birnaviral multifunctional VP3 protein and its unexplored critical roleFerrero, DiegoGiménez. María CeciliaSagar, AminRodríguez, Javier M.Castón, José R.Terebiznik, Mauricio R.Bernadó, PauVerdaguer, NúriaIBDVdsRNA-binding proteinMoonlighting proteinsScaffolding proteinViral replicationTo overcome their limited genetic capacity, numerous viruses encode multifunctional proteins. The birnavirus VP3 protein plays key roles during infection, including scaffolding of the viral capsid during morphogenesis, recruitment, and regulation of the viral RNA polymerase, shielding of the double-stranded RNA genome and targeting of host endosomes for genome replication, and immune evasion. The dimeric form of VP3 is critical for these functions. In previous work, we determined the X-ray structure of the central domains (D2–D3) of VP3 from the infectious bursal disease virus (IBDV). However, the structure and function of the IBDV VP3 N-terminal domain (D1) could not be determined at that time. Using integrated structural biology approaches and functional cell assays, here we characterize the IBDV VP3 D1 domain, unveiling its unexplored roles in virion stability and infection. The X-ray structure of D1 shows that this domain folds in four α-helices arranged in parallel dimers, which are essential for maintaining the dimeric arrangement of the full-length protein. Combining small-angle X-ray scattering analyses with molecular dynamics simulations allowed us to build a structural model for the D1–D3 domains. This model consists of an elongated structure with high flexibility in the D2–D3 connection, keeping D1 as the only driver of VP3 dimerization. Using reverse genetics tools, we show that the obliteration of D1 domain prevents the VP3 scaffold function during capsid assembly and severely impacts IBDV infection. Altogether, our study elucidates the structure of the VP3 D1 domain and reveals its role in VP3 protein dimerization and IBDV infection.The work at IBMB was funded by the Spanish Ministry of Science and Innovation (PID2020-117976GB-I00). The work at the CBS was funded by Labex EpiGenMed, an “Investissements d’avenir” program (ANR-10-LABX-12-01). The work at the CNB was supported by grants from the Spanish Ministry of Science and Innovation (PID2020-113287RB-I00) and the Comunidad Autónoma de Madrid (P2018/NMT-4389) to J.R.C. Mauricio R. Terebiznik funding to this project was provided by the Discovery Grants programs RGPIN-2018-05734 and RGPAS2018-522692 from the Natural Sciences and Engineering Research Council of Canada (NSERC). X-ray data were collected at ESRF, beamline ID29 (ESRF, Grenoble, France), and XALOC (ALBA, Cerdanyola del Vallés, Spain). SAXS data were collected at EMBL-bioSAXS P12 Beamline at Petra III storage ring (Hamburg) and BM29 BioSAXS beamline at ESRF (Grenoble). Financial support was provided by Instruct-ERIC (PID6902) for access to Hamburg synchrotron. The CBS is a member of France-BioImaging (FBI) and the French Infrastructure for Integrated Structural Biology (FRISBI), two national infrastructures supported by the French National Research Agency (ANR-10-INBS-04-01 and ANR-10-INBS-05, respectively).Peer reviewedOxford University PressNational Academy of Sciences (U.S.)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Agence Nationale de la Recherche (France)Comunidad de MadridNatural Sciences and Engineering Research Council of CanadaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/379564reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117976GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113287RB-I00S2018/NMT-4389/NANOBIOCARGO-CMThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/pnasnexus/pgae521https://doi.org/10.1093/pnasnexus/pgae521Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3795642026-05-22T06:33:51Z
score 15,812455

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