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Crystal structures of GI.8 Boxer virus P dimers in complex with HBGAs, a novel evolutionary path selected by the Lewis epitope
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  • 分类:S852.651[农业科学—基础兽医学;农业科学—兽医学;农业科学—畜牧兽医] O614.121[理学—无机化学;理学—化学]
  • 作者机构:[1]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, [2]University of Chinese Academy of Sciences, Beijing 100049, China, [3]Division of Infectious Diseasess, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA, [4]University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
  • 相关基金:The research described in this article was supported by the National Basic Research Program (973 Program) (Nos. 2011CB910304 and 2011CB915501) and the National Natural Science Foundation of China (Grant Nos. 31400639 and 31170702). The research of Xi Jiang and Ming Tan's labs is supported by the US National Institute of Health (R01 AI089634/P01 HD13021 to X.J. and R21 AI092434/ NCRR 8ULITR000077-04 to M.T.).
中文摘要:

人的 noroviruses (huNoVs ) 作为附件因素,在 genogroup (G) ,我和 GII huNoVs 使用不同有约束力的接口认出 histo 血组抗原(HBGA ) 。在由主人 HBGA 的选择下面的 GII huNoVs 的基因、进化的关系很好经由很多结构的研究被阐明了;然而,在官方补给的 11 月之中的如此的关系由于仅仅有类似的有约束力的侧面的三个官方补给的 11 月的 HBGA 有约束力的接口的结构被知道的事实仍然保持不太清楚。在水晶吊楔绑定紧张的 P dimers 组织的这研究,不绑 A 和 H 抗原的 GI.8 拳击手病毒( BV ),在有吊楔 b 的建筑群( Le <啜class=“ a-plus-plus ”> b )和 Le <啜class=“ a-plus-plus ”>分别地, y 抗原被决定并且与那些相比三以前已知的官方补给的 huNoVs ,即 GI.1 Norwalk 病毒( NV ), GI.2 FUV258 ( FUV )和绑 A/H/Le 抗原的 GI.7 TCH060 ( TCH )。 BV 的 HBGA 有约束力的接口由与先锋的半乳糖交往的一个保存中央有约束力的衣袋( CBP )组成,并且一个开发得好的 Le epitope有约束力的地点由五氨基酸形成了,包括从长P环的三连续残余和从 P1 子域的海岸炮舰的残余,没在另一方面在另外的官方补给的11月被看见的一个特征,在另外的官方补给的11月观察的 H epitope/acetamido 绑定地点极大地在 BV 被堕落。这些数据解释多态的人的 HBGA 选择的官方补给的 11 月的进化路径。当 CBP 被保存时,包围 CBP 的区域是灵活的,提供为变化的自由。H epitope/acetamido 绑定地点的损失和 GI.8 BV 的 Le 有约束力的地点的加强是主机路易斯 epitope 选择的如此的变化的一个典型例子。

英文摘要:

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as attachment factors, in which genogroup (G) I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus (BV) that does not bind the A and H antigens, in complex with the Lewis b (Le^b) and Ley antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Nor- walk virus (NV), GI.2 FUV258 (FUV) and GI.7 TCH060 (TCH) that bind the A/HILe antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket (CBP) that interacts with the β-galactose of the precursor, and a well-developed Le epitope-bind- ing site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the poly- morphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providingfreedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI,8 BV is a typical example of such change selected by the host Lewis epitope.

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