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Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus.


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. P[8] is the predominant RV genotype in humans, but the structural basis of how P[8] RVs interact with glycan ligands remains elusive. In this study, we characterized the interactions between P[8] 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 P[8] RV-glycans interaction from the crystal structures of a Rotateq P[8] VP8* in complex with core 2 and H type 1 glycans at 1.8 Å and 2.3 Å, 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 P[II] genogroup, while genotype-specific amino acid variations determined different glycan binding preference. Our data elucidated the detailed structural basis of the interactions between human P[8] RVs and different host glycan factors, shedding light on RV infection, epidemiology, and development of anti-viral agents.

SUBMITTER: Sun X 

PROVIDER: S-EPMC7198667 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus.

Sun Xiaoman X   Dang Lei L   Li Dandi D   Qi Jianxun J   Wang Mengxuan M   Chai Wengang W   Zhang Qing Q   Wang Hong H   Bai Ruixia R   Tan Ming M   Duan Zhaojun Z  

Virologica Sinica 20191016 2


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. P[8] is the predominant RV genotype in humans, but the structural basis of how P[8] RVs interact with glycan ligands remains elusive. In this study, we characterized the interactions between P[8] VP8*s and glycans which showed that VP8*, the RV glycan bindin  ...[more]

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