Structural basis for the recognition of blood group trisaccharides by norovirus
Structural basis for the recognition of blood group trisaccharides by norovirus
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DOI：
10.1128/jvi.00219-07
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Rao, Zihe
中科院分区：
文献类型：
--
作者：
Cao, Sheng;Lou, Zhiyong;Rao, Zihe
诺如病毒是人类非细菌性胃肠炎流行的主要原因之一。最近对诺如病毒受体的研究表明，不同的诺如病毒识别不同的人类组织血型抗原（HBGAs），并已确定诺如病毒的8种受体结合模式。诺如病毒衣壳的P结构域直接参与这种识别。为了确定HBGA碳水化合物在病毒衣壳上的精确位置和受体结合模式，将GII-4株诺如病毒VA 387的重组P蛋白与合成的A型或B型三聚氰胺共结晶。基于在2.0埃分辨率下观察到的复杂晶体结构，我们证明了受体结合位点位于P结构域的最外端，并与糖配体形成广泛的氢键网络。A和B三联体显示相似的结合模式，并且共同的岩藻糖环在这种相互作用中起关键作用。P二聚体中两个原聚体之间的广泛界面在受体结合界面的形成中也起着至关重要的作用。
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-angstrom 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.