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Crystal structure of P[6] rotavirus vp8* complexed with LNFPI
Structural highlights
FunctionPublication Abstract from PubMedInitial 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 alpha-helix and a beta-sheet, referred as the "betaalpha binding site", the P[8] and P[4] VP8*s bind Leb HBGAs in a previously undescribed pocket formed by the edges of two beta-sheets, referred to as the "betabeta binding site". Importantly, the P[8] and P[4] VP8*s retain binding capability to non-Leb type 1 HBGAs using the betaalpha 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. Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens.,Xu S, Ahmed LU, Stuckert MR, McGinnis KR, Liu Y, Tan M, Huang P, Zhong W, Zhao D, Jiang X, Kennedy MA PLoS Pathog. 2020 Mar 24;16(3):e1008386. doi: 10.1371/journal.ppat.1008386., eCollection 2020 Mar. PMID:32208455[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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