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Nat Commun. 2018 Jul 6;9(1):2631. doi: 10.1038/s41467-018-05098-4.

Glycan recognition in globally dominant human rotaviruses.

Author information

1
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
2
Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
3
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.
4
Department of Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
5
Department of Biochemistry and the Emory Comprehensive Glycomics Core, Emory University School of Medicine, Atlanta, GA, 30322, USA.
6
Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
7
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. vprasad@bcm.edu.
8
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA. vprasad@bcm.edu.

Abstract

Rotaviruses (RVs) cause life-threatening diarrhea in infants and children worldwide. Recent biochemical and epidemiological studies underscore the importance of histo-blood group antigens (HBGA) as both cell attachment and susceptibility factors for the globally dominant P[4], P[6], and P[8] genotypes of human RVs. How these genotypes interact with HBGA is not known. Here, our crystal structures of P[4] and a neonate-specific P[6] VP8*s alone and in complex with H-type I HBGA reveal a unique glycan binding site that is conserved in the globally dominant genotypes and allows for the binding of ABH HBGAs, consistent with their prevalence. Remarkably, the VP8* of P[6] RVs isolated from neonates displays subtle structural changes in this binding site that may restrict its ability to bind branched glycans. This provides a structural basis for the age-restricted tropism of some P[6] RVs as developmentally regulated unbranched glycans are more abundant in the neonatal gut.

PMID:
29980685
PMCID:
PMC6035239
DOI:
10.1038/s41467-018-05098-4
[Indexed for MEDLINE]
Free PMC Article

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