Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography

By Liya Hu, W. Salmen, B. Sankaran, Yi Lasanajak, David F. Smith, S. Crawford, M. Estes, B. Prasad. 2022

18 citations recorded by the source corpus.

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. Group B rotaviruses have a unique fold in the glycan-binding domain specific for N- acetyllactosamine that potentially diverged from folds conserved in group A and C rotaviruses.

Subfields: Endocrinology, Infectious Diseases

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1. Yi Zhao
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Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, methodology): “For example, Hu et al. 70 utilized X-ray crystallography and AF2 prediction to determine the structure of the VP8* domain (VP8*B) of VP4, which is a spike protein, in group B rotaviruses.”