Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, People's Republic of China.
PLoS One. 2012;7(6):e38794. doi: 10.1371/journal.pone.0038794. Epub 2012 Jun 14.
Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.
越来越多的 H5N1 流感病毒（IVs）导致人类死亡，尤其是在北非和东南亚。病毒表面的血凝素（HA）与宿主唾液酸（SA）受体的结合是感染过程中的一个必要步骤。系统发育分析显示，根据 HA 序列，H5N1 病毒可分为 10 个分支，大多数人类 IV 集中在分支 1 和分支 2.1 到分支 2.3。不同分支中的蛋白序列比对表明，受体结合域（RBD）的高度保守对于与 SA 受体结合至关重要。两个糖基化位点 158N 和 169N 也参与受体识别。在本工作中，我们试图构建一系列包含多种糖基化 HA 的 H5N1 HA 模型，以在计算机中模拟与各种 SA 受体的结合过程。由于 SA-α-2,3-Gal 和 SA-α-2,6-Gal 受体分别采用直形和鱼钩形两种独特的拓扑结构，因此 158N 位的 N-糖基化会降低 HA 与所有受体的亲和力，尤其是 SA-α-2,6-Gal 类似物。另一个糖基化位点 169N 位于相邻的 HA 单体上，其巨大糖基的空间位阻会更有效地阻止 SA-α-2,3-Gal 类似物的结合。
