Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens

• DOI: 10.1371/journal.ppat.1008386
• Publication Date: 2020-03-24T17:36:52Z
• Authors: Shenyuan Xu; Luay U. Ahmed; Michael Robert St...; Kristen Rose McGi...; Yang Liu; Ming Tan; Pengwei Huang; Weiming Zhong; Dandan Zhao; Xi Jiang; Michael A. Kennedy
• Keywords: Protein Conformation, alpha-Helical; Rotavirus; 0301 basic medicine; QH301-705.5; Immunology; RC581-607; Microbiology; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Lewis Blood Group Antigens; Virology; Genetics; Humans; Capsid Proteins; Protein Conformation, beta-Strand; Parasitology; Immunologic diseases. Allergy; Biology (General); HT29 Cells; Molecular Biology; Research Article

Initial cell attachment of rotavirus (RV) to specific surface glycan receptors, which is the essential first step in RV infection, mediated by VP8* domain spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or factors for strains. strains P[4] and P[8] genotypes P[II] genogroup share common recognition Lewis b (Leb) H type 1 antigens, however, molecular basis receptor major RVs remains unknown due lack experimental structural information. Here, we used nuclear magnetic resonance (NMR) spectroscopy-based titration experiments NMR-derived high ambiguity driven docking (HADDOCK) methods elucidate Leb (LNDFH I) HBGAs. We also X-ray crystallography determine details underlying P[6] Unlike P[6]/P[19] VP8*s that recognize HBGAs a binding composed an α-helix β-sheet, referred “βα site”, bind previously undescribed pocket formed edges two β-sheets, “ββ site”. Importantly, retain capability non-Leb using βα site. The presence distinct sites HBGA glycans domains suggests host-pathogen co-evolution under functional adaptation pathogens host polymorphisms. Assessment understanding precise impact this co-evolutionary process determining ranges cross-species transmission should facilitate improved vaccine development prediction future strain emergence epidemics.