Crystal Structure of the Human Astrovirus Capsid Protein

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dc.citation.firstpage9008
dc.citation.issueNumber20
dc.citation.journalTitleJournal of Virology
dc.citation.lastpage9017
dc.citation.volumeNumber90
dc.contributor.authorToh, Yukimatsu
dc.contributor.authorHarper, Justin
dc.contributor.authorDryden, Kelly A.
dc.contributor.authorYeager, Mark
dc.contributor.authorArias, Carlos F.
dc.contributor.authorMéndez, Ernesto
dc.contributor.authorTao, Yizhi Jane
dc.date.accessioned2017-05-15T21:11:38Z
dc.date.available2017-05-15T21:11:38Z
dc.date.issued2016
dc.description.abstractHuman astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. HAstV is a nonenveloped virus with a T=3 capsid and a positive-sense RNA genome. The capsid protein (CP) of HAstV is synthesized as a 90-kDa precursor (VP90) that can be divided into three linear domains: a conserved N-terminal domain, a hypervariable domain, and an acidic C-terminal domain. Maturation of HAstV requires proteolytic processing of the astrovirus CP both inside and outside the host cell, resulting in the removal of the C-terminal domain and the breakdown of the rest of the CP into three predominant protein species with molecular masses of ∼34, 27/29, and 25/26 kDa, respectively. We have now solved the crystal structure of VP9071–415 (amino acids [aa] 71 to 415 of VP90) of human astrovirus serotype 8 at a 2.15-Å resolution. VP9071–415 encompasses the conserved N-terminal domain of VP90 but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP9071–415 is comprised of two domains: an S domain, which adopts the typical jelly-roll β-barrel fold, and a P1 domain, which forms a squashed β-barrel consisting of six antiparallel β-strands similar to what was observed in the hepatitis E virus (HEV) capsid structure. Fitting of the VP9071–415 structure into the cryo-electron microscopy (EM) maps of HAstV produced an atomic model for a continuous, T=3 icosahedral capsid shell. Our pseudoatomic model of the human HAstV capsid shell provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation needed for virus infectivity. Such information has potential applications in the development of a virus-like particle (VLP) vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation.
dc.identifier.citationToh, Yukimatsu, Harper, Justin, Dryden, Kelly A., et al.. "Crystal Structure of the Human Astrovirus Capsid Protein." <i>Journal of Virology,</i> 90, no. 20 (2016) American Association for Microbiology: 9008-9017. https://doi.org/10.1128/JVI.00694-16.
dc.identifier.doihttps://doi.org/10.1128/JVI.00694-16
dc.identifier.urihttps://hdl.handle.net/1911/94276
dc.language.isoeng
dc.publisherAmerican Association for Microbiology
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCrystal Structure of the Human Astrovirus Capsid Protein
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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