Differences in glycan binding specificities among Rotavirus-A, -B, and -C

A group from Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX USA, etc. has reported about folding structures of rotavirus spike protein VP4 and the difference in those glycan binding specificities.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072675/

Rotaviruses are classified into ten different species or groups (A–J). Group A, B, C, and H rotaviruses infect both humans and animals. Epidemiologically, groups A, B, and C are the best characterized. Group A rotaviruses (RVA) and to a lesser extent group C rotaviruses (RVC) are the causative agents of most gastroenteric infections worldwide, the group B rotaviruses (RVB) have been associated with large epidemic outbreaks of severe gastroenteritis in China and sporadic infection in several countries.

The viral genome consists of 11 segments of double-stranded RNA that code for 6 structural viral proteins (VP) and 6 nonstructural proteins. The infectious virion is a triple-layered particle consisting of a core layer made of VP2, an intermediate layer made of VP6, and an outer shell made of glycoprotein VP7. Sixty protein spikes made of a protease-sensitive protein, VP4, extend from the VP7 shell.

The proteolytic treatment of VP4 results in two fragments, VP8* and VP5*. Sequence comparison of the structural proteins encoded by different rotavirus groups shows that the VP8* domain of the spike protein VP4 is the most variable. Extensive structural studies have shown that there is a galectin-like domain in human RVA and RVC (VP8*A and VP8*C), and recognize various cellular glycans in a genotype-dependent manner. The most typical glycan binding specificity of VP8*A and VP8*C are known to be H-antigen and A-antigen respectively.

Interestingly, the VP8*B shares no sequence identity with either VP8*A or VP8*C, which could differentially impact not only the structure but also the glycan-binding properties. Authors have found that VP8*B exhibits a fold with a twisted β-sheet clasping an α-helix that is entirely different from VP8*A or VP8*C, and glycan array screening and in silico docking analysis show VP8*B recognizes glycans containing LacNAc.