title: Novel structural insights into rotavirus recognition of ganglioside glycan receptors.
abstract: Rotaviruses ubiquitously infect children under the age of 5, being responsible for more than half a million diarrhoeal deaths each year worldwide. Host cell oligosaccharides containing sialic acid(s) are critical for attachment by rotaviruses. However, to date, no detailed three-dimensional atomic model showing the exact rotavirus interactions with these glycoconjugate receptors has been reported. Here, we present the first crystallographic structures of the rotavirus carbohydrate-recognizing protein VP8* in complex with ganglioside G(M3) glycans. In combination with assessment of the inhibition of rotavirus infectivity by N-acetyl and N-glycolyl forms of this ganglioside, our results reveal key details of rotavirus-ganglioside G(M3) glycan recognition. In addition, they show a direct correlation between the carbohydrate specificities exhibited by VP8* from porcine and by monkey rotaviruses and the respective infectious virus particles. These novel results also indicate the potential binding interactions of rotavirus VP8* with other sialic acid-containing gangliosides.
authors.affiliation: Institute for Glycomics, Gold Coast campus, Griffith University, Queensland 4222, Australia.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Coulson
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Fleming
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
authors.forename: Helen
authors.initials: H
authors.lastname: Blanchard
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000378:metabolism*; D000882:Haplorhini; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D012401:Rotavirus / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000378:metabolism* / Q000821:virology; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D011134:Polysaccharides; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus; D019158:N-Acetylneuraminic Acid