title: Affinities of recombinant norovirus P dimers for human blood group antigens.
abstract: Noroviruses (NoVs), the major cause of viral acute gastroenteritis, recognize histo-blood group antigens (HBGAs) as receptors or attachment factors. To gain a deeper understanding of the interplay between NoVs and their hosts, the affinities of recombinant P dimers (P₂'s) of a GII.4 NoV (VA387) to a library of 41 soluble analogs of HBGAs were measured using the direct electrospray ionization mass spectrometry assay. The HBGAs contained the A, B, H and Lewis epitopes, with variable sizes (2-6 residues) and different types (1-6). The results reveal that the P₂'s exhibit a broad specificity for the HBGAs and bind to all of the oligosaccharides tested. Overall, the affinities are relatively low, ranging from 400 to 3000 M⁻¹ and are influenced by the chain type: 3 > 1 ≈ 2 ≈ 4 ≈ 5 ≈ 6 for H antigens; 6 > 1 ≈ 3 ≈ 4 ≈ 5 > 2 for A antigens; 3 > 1 ≈ 4 ≈ 5 ≈ 6 > 2 for B antigens, but not by chain length. The highest-affinity ligands are B type 3 (3000 ± 300 M⁻¹) and A type 6 (2350 ± 60 M⁻¹). While the higher affinity to the type 3 H antigen was previously observed, preferential binding to the types 6 and 3 antigens with A and B epitopes, respectively, has not been previously reported. A truncated P domain dimer (lacking the C-terminal arginine cluster) exhibits similar binding. The central-binding motifs in the HBGAs were identified by molecular-docking simulations.
authors.affiliation: Department of Chemistry, Alberta Glycomics Centre, University of Alberta, Edmonton, AB T6G 2G2, Canada.
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Kitov
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kitova
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Leyi
authors.initials: L
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: John S
authors.initials: JS
authors.lastname: Klassen
mesh_terms: D001665:Binding Sites; D001789:Blood Group Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D029322:Norovirus / Q000737:chemistry / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011991:Receptors, Virus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001789:Blood Group Antigens; D000939:Epitopes; D009844:Oligosaccharides; D011991:Receptors, Virus; D014764:Viral Proteins