Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

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dc.contributor University of Helsinki, Institute of Biotechnology en
dc.contributor University of Helsinki, Institute of Biotechnology en
dc.contributor University of Helsinki, Biosciences en
dc.contributor.author Shakeel, Shabih
dc.contributor.author Westerhuis, Brenda M.
dc.contributor.author Domanska, Ausra
dc.contributor.author Koning, Roman I.
dc.contributor.author Matadeen, Rishi
dc.contributor.author Koster, Abraham J.
dc.contributor.author Bakker, Arjen Q.
dc.contributor.author Beaumont, Tim
dc.contributor.author Wolthers, Katja C.
dc.contributor.author Butcher, Sarah Jane
dc.date.accessioned 2016-08-16T13:46:02Z
dc.date.available 2016-08-16T13:46:02Z
dc.date.issued 2016-07-20
dc.identifier.citation Shakeel , S , Westerhuis , B M , Domanska , A , Koning , R I , Matadeen , R , Koster , A J , Bakker , A Q , Beaumont , T , Wolthers , K C & Butcher , S J 2016 , ' Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis ' , Nature Communications , vol. 7 , 11387 . https://doi.org/10.1038/ncomms11387 en
dc.identifier.issn 2041-1723
dc.identifier.other PURE: 67108601
dc.identifier.other PURE UUID: ac0bb6f7-628f-4838-b2e3-8282dbb2edd2
dc.identifier.other Scopus: 84979600171
dc.identifier.other WOS: 000380833400001
dc.identifier.other ORCID: /0000-0002-3772-6003/work/40014035
dc.identifier.other ORCID: /0000-0001-7060-5871/work/28762407
dc.identifier.other ORCID: /0000-0003-3651-6087/work/30225932
dc.identifier.uri http://hdl.handle.net/10138/165877
dc.description.abstract The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation. en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights en
dc.subject 1182 Biochemistry, cell and molecular biology en
dc.subject VIROLOGY en
dc.subject CRYO-ELECTRON MICROSCOPY en
dc.subject STRUCTURAL BIOLOGY en
dc.subject SINGLE PARTICLE en
dc.subject PICORNAVIRUSES en
dc.subject PARECHOVIRUS en
dc.subject 1183 Plant biology, microbiology, virology en
dc.title Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/ncomms11387
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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