Novel Fold of Rotavirus Glycan-Binding Domain Predicted by AlphaFold2 and Determined by X-Ray Crystallography

Authors

Liya Hu
Wilhelm Salmen
Banumathi Sankaran
Yi Lasanajak
David F Smith
Sue E Crawford
Mary K Estes
B V Venkataram Prasad

Publication Date

5-5-2022

Journal

Communications Biology

DOI

10.1038/s42003-022-03357-1

PMID

35513489

PMCID

PMC9072675

PubMedCentral® Posted Date

5-5-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Capsid Proteins, Child, Crystallography, X-Ray, Galectins, Humans, Polysaccharides, Rotavirus, X-ray crystallography, Biochemistry

Abstract

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping an α-helix represents a new fold for glycan recognition based on glycan array screening, which shows that VP8*B recognizes glycans containing N-acetyllactosamine moiety. Although uncommon, our study illustrates how evolution can incorporate structurally distinct folds with similar functionality in a homologous protein within the same virus genus.