Crystal Structure of the Human Astrovirus Capsid Protein

Journal Article · Wed Jul 27 00:00:00 EDT 2016 · Journal of Virology

DOI:https://doi.org/10.1128/JVI.00694-16· OSTI ID:1438862

Toh, Yukimatsu ^[1]; Harper, Justin ^[1]; Dryden, Kelly A. ^[2]; Yeager, Mark ^[2]; Arias, Carlos F.  ^[3]; Méndez, Ernesto ^[3]; Tao, Yizhi J. ^[1]

---

1. Rice Univ., Houston, TX (United States)
2. Univ. of Virginia School of Medicine, Charlottesville, VA (United States)
3. Univ. Nacional Autonoma de México, Cuernavaca, Morelos (Mexico)

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 VP90^71–415 (amino acids [aa] 71 to 415 of VP90) of human astrovirus serotype 8 at a 2.15-Å resolution. VP90^71–415 encompasses the conserved N-terminal domain of VP90 but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP90^71–415 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 VP90^71–415 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.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: Welch Foundation; National Institutes of Health (NIH); US Department of Health and Human Services
• Grant/Contract Number: AI103777; GM066087; C-1565
• OSTI ID: 1438862
• Journal Information: Journal of Virology, Vol. 90, Issue 20; ISSN 0022-538X
• Publisher: American Society for Microbiology
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES