Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus

• DOI: 10.1128/jvi.00219-07
• Publication Date: 2007-03-29T00:33:47Z
• Authors: Sheng Cao; Zhiyong Lou; Ming Tan; Yutao Chen; Yijin Liu; Zhushan Zhang; Xuejun C. Zhang; Xi Jiang; Xuemei Li; Zihe Rao
• Keywords: Oligosaccharides, Branched-Chain; 0301 basic medicine; Molecular Sequence Data; Norovirus; Oligosaccharides; Crystallography, X-Ray; ABO Blood-Group System; Protein Structure, Tertiary; 3. Good health; 03 medical and health sciences; Receptors, Virus; Capsid Proteins; Amino Acid Sequence; Crystallization; Trisaccharides

ABSTRACT Noroviruses are one of the major causes of nonbacterial gastroenteritis epidemics in humans. Recent studies on norovirus receptors show that different noroviruses recognize different human histo-blood group antigens (HBGAs), and eight receptor binding patterns of noroviruses have been identified. The P domain of the norovirus capsids is directly involved in this recognition. To determine the precise locations and receptor binding modes of HBGA carbohydrates on the viral capsids, a recombinant P protein of a GII-4 strain norovirus, VA387, was cocrystallized with synthetic type A or B trisaccharides. Based on complex crystal structures observed at a 2.0-Å resolution, we demonstrated that the receptor binding site lies at the outermost end of the P domain and forms an extensive hydrogen-bonding network with the saccharide ligand. The A and B trisaccharides display similar binding modes, and the common fucose ring plays a key role in this interaction. The extensive interface between the two protomers in a P dimer also plays a crucial role in the formation of the receptor binding interface.