Hao Ning, Chen Yutao, Xia Ming, Tan Ming, Liu Wu, Guan Xiaotao, Jiang Xi, Li Xuemei, Rao Zihe
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Protein Cell. 2015 Feb;6(2):101-16. doi: 10.1007/s13238-014-0126-0. Epub 2014 Dec 31.
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 Le(y) antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Norwalk virus (NV), GI.2 FUV258 (FUV) and GI.7 TCH060 (TCH) that bind the A/H/Le 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-binding 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 polymorphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providing freedom 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.
人诺如病毒（huNoVs）将组织血型抗原（HBGAs）识别为附着因子，其中基因群（G）I和GII的huNoVs使用不同的结合界面。通过大量结构研究，宿主HBGAs选择下的GII huNoVs的遗传和进化关系已得到充分阐明；然而，由于仅知道三种具有相似结合谱的GI诺如病毒的HBGA结合界面结构，GI诺如病毒之间的这种关系仍不太清楚。在本研究中，分别测定了不结合A和H抗原的Lewis结合株GI.8拳击手病毒（BV）的P二聚体与Lewis b（Le(b)）和Le(y)抗原形成复合物的晶体结构，并与之前已知的三种GI huNoVs，即结合A/H/Le抗原的GI.1诺沃克病毒（NV）、GI.2 FUV258（FUV）和GI.7 TCH060（TCH）的晶体结构进行了比较。BV的HBGA结合界面由一个与前体的β-半乳糖相互作用的保守中央结合口袋（CBP）和一个由五个氨基酸形成的发育良好的Le表位结合位点组成，其中包括来自P1亚结构域长P环的三个连续残基和一个来自S环的残基，这一特征在其他GI诺如病毒中未见。另一方面，在其他GI诺如病毒中观察到的H表位/乙酰氨基结合位点在BV中大大退化。这些数据解释了由多态性人类HBGAs选择的GI诺如病毒的进化路径。虽然CBP是保守的，但CBP周围的区域是灵活的，为变化提供了自由度。GI.8 BV的H表位/乙酰氨基结合位点的丧失或退化以及Le结合位点的加强是宿主Lewis表位选择的这种变化的典型例子。
