| Abstract: | Rotavirus (RV) causes acute gastroenteritis in infants and children worldwide. Recent studies showed that glycans such as histo-blood group antigens (HBGAs) function as cell attachment factors affecting RV host susceptibility and prevalence. P8] is the predominant RV genotype in humans, but the structural basis of how P8] RVs interact with glycan ligands remains elusive. In this study, we characterized the interactions between P8] VP8*s and glycans which showed that VP8*, the RV glycan binding domain, recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays. Importantly, we determined the structural basis of P8] RV-glycans interaction from the crystal structures of a Rotateq P8] VP8* in complex with core 2 and H type 1 glycans at 1.8? and 2.3?, respectively, revealing a common binding pocket and similar binding mode. Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the PII] genogroup, while genotype-specific amino acid variations determined different glycan binding preference. Our data elucidated the detailed structural basis of the interactions between human P8] RVs and different host glycan factors, shedding light on RV infection, epidemiology, and development of anti-viral agents. |
