Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, CA, USA.
Commun Biol. 2022 May 5;5(1):419. doi: 10.1038/s42003-022-03357-1.
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 (VP8B) 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 VP8B 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 VP8B 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.
A、C 组轮状病毒的 Spike 蛋白 VP4 的 VP8结构域，在细胞进入过程中识别聚糖时表现出保守的半乳糖凝集素样折叠。在引起成人严重腹泻暴发的 B 组轮状病毒中，VP8结构域（VP8B）出人意料地缺乏与 A 组或 C 组轮状病毒的 VP8的序列相似性。在这里，我们使用最近开发的 AlphaFold2 进行从头预测结构，并通过确定 1.3 Å 的晶体结构来验证预测模型，结果表明 VP8B 表现出一种与半乳糖凝集素折叠不同的新型折叠。这种带有β-折叠扣住α-螺旋的折叠代表了一种基于聚糖阵列筛选的新型聚糖识别折叠，其表明 VP8B 识别含有 N-乙酰乳糖胺部分的聚糖。尽管不常见，但我们的研究说明了进化如何在同一病毒属的同源蛋白中纳入具有相似功能的结构上截然不同的折叠。
