crystallography of a lewis-binding norovirus, elucidation of strain-specificity to the polymorphic human histo-blood group antigens结晶学的lewis-binding诺瓦克病毒,说明人类histo-blood组抗原strain-specificity的多态.pdfVIP

Crystallography of a Lewis-Binding Norovirus, Elucidation of Strain-Specificity to the Polymorphic Human Histo-Blood Group Antigens Yutao Chen1., Ming Tan2,3., Ming Xia2, Ning Hao 1, Xuejun C. Zhang 1, Pengwei Huang2, Xi Jiang2,3*, Xuemei Li1*, Zihe Rao 1 1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, 2 Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, 3 University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America 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 Ley or sialyl Lex 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 a-1, 3 fucose (the Lewis epitope) as major and the b-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