Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg 69120, Germany; Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg 69120, Germany.
European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, Grenoble, F-38042, France; Unit for Virus Host Cell Interactions, Univ. Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, Grenoble F-38042, France.
Virology. 2015 Sep;483:203-8. doi: 10.1016/j.virol.2015.04.006. Epub 2015 May 15.
Human noroviruses bind histo-blood group antigens (HBGAs) and this interaction is thought to be important for an infection. We identified two additional fucose-binding pockets (termed fucose-3/4 sites) on a genogroup II human (GII.10) norovirus-protruding (P) dimer using X-ray crystallography. Fucose-3/4 sites were located between two previously determined HBGA binding pockets (termed fucose-1/2 sites). We found that four fucose molecules were capable of binding altogether at fucose-1/2/3/4 sites on the P dimer, though the fucose molecules bound in a dose-dependent and step-wise manner. We also showed that HBGA B-trisaccharide molecules bound in a similar way at the fucose-1/2 sites. Interestingly, we discovered that the monomers of the P dimer were asymmetrical in an unliganded state and when a single B-trisaccharide molecule bound, but were symmetrical when two B-trisaccharide molecules bound. We postulate that the symmetrical dimers might favor HBGA binding interactions at fucose-1/2 sites.
人类诺如病毒结合组织血型抗原（HBGAs），这种相互作用被认为对感染很重要。我们使用 X 射线晶体学在一个基因 II 组（GII.10）人类诺如病毒突出（P）二聚体上鉴定了另外两个岩藻糖结合口袋（称为岩藻糖 3/4 结合位点）。岩藻糖 3/4 结合位点位于两个先前确定的 HBGA 结合口袋（称为岩藻糖 1/2 结合位点）之间。我们发现，四个岩藻糖分子总共可以在 P 二聚体上的岩藻糖 1/2/3/4 结合位点结合，但岩藻糖分子以剂量依赖和逐步的方式结合。我们还表明，HBGA B-三糖分子以类似的方式在岩藻糖 1/2 结合位点结合。有趣的是，我们发现未配体结合状态下的 P 二聚体单体是不对称的，当一个 B-三糖分子结合时，单体是不对称的，但当两个 B-三糖分子结合时，单体是对称的。我们推测对称二聚体可能有利于在岩藻糖 1/2 结合位点上进行 HBGA 结合相互作用。
