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

Xu, Shenyuan; Ahmed, Luay U.; Stuckert, Michael Robert; McGinnis, Kristen Rose; Liu, Yang; Tan, Ming; Huang, Pengwei; Zhong, Weiming; Zhao, Dandan; Jiang, Xi; Kennedy, Michael A.

doi:10.1371/journal.ppat.1008386

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

Journal Article · Tue Mar 24 00:00:00 EDT 2020 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1008386· OSTI ID:1618487

Xu, Shenyuan ^[1];

^[1];

^[1]; McGinnis, Kristen Rose ^[1]; Liu, Yang ^[2]; Tan, Ming ^[3];

^[3]; Zhong, Weiming ^[3]; Zhao, Dandan ^[3]; Jiang, Xi ^[4];

^[1]

Miami Univ., Oxford, OH (United States)
Cincinnati Children's Hospital Medical Center, Cincinnati, OH (United States); Chinese Academy of Medical Sciences, Tianjin (China)
Cincinnati Children's Hospital Medical Center, Cincinnati, OH (United States)
Cincinnati Children's Hospital Medical Center, Cincinnati, OH (United States); Univ. of Cincinnati, OH (United States)

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 (Le^b) 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 α-helix and a β-sheet, referred as the “βα binding site”, the P[8] and P[4] VP8*s bind Le^b HBGAs in a previously undescribed pocket formed by the edges of two β-sheets, referred to as the “ββ binding site”. Importantly, the P[8] and P[4] VP8*s retain binding capability to non-Le^b type 1 HBGAs using the βα binding site. The presence of two distinct binding sites for Le^b and non-Le^b 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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI ID:: 1618487

Journal Information:: PLoS Pathogens, Vol. 16, Issue 3; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 18 works

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