%0 Journal Article
%T Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens
%A Dandan Zhao
%A Kristen Rose McGinnis
%A Luay U. Ahmed
%A Michael A. Kennedy
%A Michael Robert Stuckert
%A Ming Tan
%A Pengwei Huang
%A Shenyuan Xu
%A Weiming Zhong
%A Xi Jiang
%A Yang Liu
%J -
%D 2020
%R 10.1371/journal.ppat.1008386
%X Initial cell attachment of rotavirus (RV) to specific cell surface glycan receptors, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b (Leb) and H type 1 antigens, however, the molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) spectroscopy-based titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb (LNDFH I) and type 1 HBGAs. We also used X-ray crystallography to determine the molecular details underlying P[6] recognition of H type 1 HBGAs. Unlike P[6]/P[19] VP8*s that recognize H type 1 HBGAs in a binding surface composed of an ¦Á-helix and a ¦Â-sheet, referred as the ¡°¦Â¦Á binding site¡±, the P[8] and P[4] VP8*s bind Leb HBGAs in a previously undescribed pocket formed by the edges of two ¦Â-sheets, referred to as the ¡°¦Â¦Â binding site¡±. Importantly, the P[8] and P[4] VP8*s retain binding capability to non-Leb type 1 HBGAs using the ¦Â¦Á binding site. The presence of two distinct binding sites for Leb and non-Leb HBGA glycans in the P[8] and P[4] VP8* domains suggests host-pathogen co-evolution under structural and functional adaptation of RV pathogens to host glycan polymorphisms. Assessment and understanding of the precise impact of this co-evolutionary process in determining RV host ranges and cross-species RV transmission should facilitate improved RV vaccine development and prediction of future RV strain emergence and epidemics
%K NMR spectroscopy
%K Crystal structure
%K Protons
%K Rotavirus infection
%K Antigen processing and recognition
%K Nuclear magnetic resonance
%K Binding analysis
%K Sequence alignment
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008386