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

• Main Authors: Crawford, S.E (Author), Estes, M.K (Author), Hu, L. (Author), Lasanajak, Y. (Author), Prasad, B.V.V (Author), Salmen, W. (Author), Sankaran, B. (Author), Smith, D.F (Author)
• Format: Article
• Language: English
• Published: Nature Research 2022
• Online Access: View Fulltext in Publisher

 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. © 2022, The Author(s).