title: Crystal structure of the human astrovirus capsid spike.
abstract: Astroviruses are single-stranded, plus-sense RNA viruses that infect both mammals and birds, causing gastroenteritis and other extraintestinal diseases. Clinical studies have established astroviruses as the second leading cause of viral diarrhea in young children. Here we report the crystal structure of the human astrovirus dimeric surface spike determined to 1.8-Å resolution. The overall structure of each spike/projection domain has a unique three-layered β-sandwiches fold, with a core, six-stranded β-barrel structure that is also found in the hepatitis E virus capsid protrusions, suggesting a closer phylogenetic relationship between these two viruses than previously acknowledged. Based on a hepatitis E virus capsid model, we performed homology modeling and produced a complete, T = 3 astrovirus capsid model with features remarkably similar to those observed in a cryoelectron microscopy reconstruction image of a human astrovirus. Mapping conserved residues onto the astrovirus projection domain revealed a putative receptor binding site with amino acid compositions characteristic for polysaccharide recognition. Our results will have an important impact on future characterization of astrovirus structure and function, and will likely have practical applications in the development of vaccines and antivirals.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, MS140, Houston, TX 77005, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Dong
authors.forename: Liping
authors.initials: L
authors.lastname: Dong
authors.forename: Ernesto
authors.initials: E
authors.lastname: Méndez
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Tao
mesh_terms: D052676:Avastrovirus / Q000737:chemistry* / Q000187:drug effects / Q000254:growth & development; D018938:Caco-2 Cells; D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D020285:Cryoelectron Microscopy; D003460:Crystallization; D016264:Dextran Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D036022:Capsid Proteins; D016264:Dextran Sulfate; D006497:Heparan Sulfate; D021122:Protein Subunits; D011994:Recombinant Proteins