Title: Crystal Structure of the Human Astrovirus Capsid Protein

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 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 virusmore » (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.« less

Authors:

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

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Méndez, Ernesto ^[3]; Tao, Yizhi J. ^[1]

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+ Show Author Affiliations

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)

Publication Date:

Wed Jul 27 00:00:00 EDT 2016

Research Org.:

Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:

Welch Foundation; National Institutes of Health (NIH); US Department of Health and Human Services

OSTI Identifier:

1438862

Grant/Contract Number:  

AI103777; GM066087; C-1565

Resource Type:

Journal Article: Accepted Manuscript

Journal Name:

Journal of Virology

Additional Journal Information:

Journal Volume: 90; Journal Issue: 20; Journal ID: ISSN 0022-538X

Publisher:

American Society for Microbiology

Country of Publication:

United States

Language:

ENGLISH

Subject:

59 BASIC BIOLOGICAL SCIENCES