6OAI

Crystal structure of P[6] rotavirus vp8* complexed with LNFPI

Summary for 6OAI

• Entry DOI: 10.2210/pdb6oai/pdb
• Descriptor: Protease-sensitive outer capsid protein, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: rotavirus, host receptor interaction, virus
• Biological source: Human rotavirus A
• Total number of polymer chains: 4
• Total formula weight: 74627.76

Authors

Xu, S.,Liu, Y.,Jiang, X.,Kennedy, M.A. (deposition date: 2019-03-16, release date: 2020-03-18, Last modification date: 2023-10-11)

Primary citation

Xu, S.,Ahmed, L.U.,Stuckert, M.R.,McGinnis, K.R.,Liu, Y.,Tan, M.,Huang, P.,Zhong, W.,Zhao, D.,Jiang, X.,Kennedy, M.A.
Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens.
Plos Pathog., 16:e1008386-e1008386, 2020

PubMed Abstract: 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 α-helix and a β-sheet, referred as the "βα binding site", the P[8] and P[4] VP8*s bind Leb 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-Leb type 1 HBGAs using the βα 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.

PubMed: 32208455
DOI: 10.1371/journal.ppat.1008386

Experimental method

X-RAY DIFFRACTION (1.9 Å)