title: Crystallography of a Lewis-binding norovirus, elucidation of strain-specificity to the polymorphic human histo-blood group antigens.
abstract: Noroviruses, an important cause of acute gastroenteritis in humans, recognize the histo-blood group antigens (HBGAs) as host susceptible factors in a strain-specific manner. The crystal structures of the HBGA-binding interfaces of two A/B/H-binding noroviruses, the prototype Norwalk virus (GI.1) and a predominant GII.4 strain (VA387), have been elucidated. In this study we determined the crystal structures of the P domain protein of the first Lewis-binding norovirus (VA207, GII.9) that has a distinct binding property from those of Norwalk virus and VA387. Co-crystallization of the VA207 P dimer with Le(y) or sialyl Le(x) tetrasaccharides showed that VA207 interacts with these antigens through a common site found on the VA387 P protein which is highly conserved among most GII noroviruses. However, the HBGA-binding site of VA207 targeted at the Lewis antigens through the α-1, 3 fucose (the Lewis epitope) as major and the β-N-acetyl glucosamine of the precursor as minor interacting sites. This completely differs from the binding mode of VA387 and Norwalk virus that target at the secretor epitopes. Binding pocket of VA207 is formed by seven amino acids, of which five residues build up the core structure that is essential for the basic binding function, while the other two are involved in strain-specificity. Our results elucidate for the first time the genetic and structural basis of strain-specificity by a direct comparison of two genetically related noroviruses in their interaction with different HBGAs. The results provide insight into the complex interaction between the diverse noroviruses and the polymorphic HBGAs and highlight the role of human HBGA as a critical factor in norovirus evolution.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.forename: Ning
authors.initials: N
authors.lastname: Hao
authors.forename: Xuejun C
authors.initials: XC
authors.lastname: Zhang
authors.forename: Pengwei
authors.initials: P
authors.lastname: Huang
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000737:chemistry* / Q000378:metabolism; D029322:Norovirus / Q000737:chemistry* / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; D009844:Oligosaccharides; D014764:Viral Proteins