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dc.contributor.authorToh, Yukimatsu
Harper, Justin
Dryden, Kelly A.
Yeager, Mark
Arias, Carlos F.
Méndez, Ernesto
Tao, Yizhi J.
dc.date.accessioned 2017-05-15T21:11:38Z
dc.date.available 2017-05-15T21:11:38Z
dc.date.issued 2016
dc.identifier.citation Toh, Yukimatsu, Harper, Justin, Dryden, Kelly A., et al.. "Crystal Structure of the Human Astrovirus Capsid Protein." Journal of Virology, 90, no. 20 (2016) American Association for Microbiology: 9008-9017. https://doi.org/10.1128/JVI.00694-16.
dc.identifier.urihttps://hdl.handle.net/1911/94276
dc.description.abstract Human 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.language.iso eng
dc.publisher American Association for Microbiology
dc.rights This 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.title Crystal Structure of the Human Astrovirus Capsid Protein
dc.type Journal article
dc.citation.journalTitle Journal of Virology
dc.citation.volumeNumber 90
dc.citation.issueNumber 20
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1128/JVI.00694-16
dc.identifier.pmcid PMC5044835
dc.identifier.pmid 27466429
dc.type.publication publisher version
dc.citation.firstpage 9008
dc.citation.lastpage 9017


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