Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments.
Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments.
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DOI：
10.1016/s0969-2126(96)00021-4
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发表时间：
1996-02
期刊：
影响因子：
5.7
通讯作者：
Thilo Stehle;Stephen C. Harrison
中科院分区：
文献类型：
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作者：
Thilo Stehle;Stephen C. Harrison
背景：鼠多瘤病毒识别易感细胞表面的（α 2，3）-连接的α-5-N-乙酰神经氨酸（唾液酸）。虽然所有菌株都与终止于（α 2，3）-连接唾液酸的直链受体结合，但一些菌株还与携带第二个（α 2，6）-连接唾液酸的支链寡糖结合。结合这些支链受体的能力与一个单一的氨基酸突变的主要衣壳蛋白，VP 1的外表面上的位置91，并与显着降低tumorigenicity.ResultsWe已确定的结构的多瘤病毒株P16，它带有一个甘氨酸在位置91，在复杂的模型化合物的直链和支链sialoglycoconjugates。结构已被细化到3.65 μ m的分辨率。配体结合到VP 1表面上的浅槽。两种化合物共有的唾液酸-（α 2，3）-半乳糖部分具有特异性和相同的接触。支链受体片段的额外（α 2，6）-连接的唾液酸部分适合表面口袋，但它具有高热因子，并且不会与VP 1上的基团形成氢键。从浸泡在不同的寡糖浓度的晶体收集的数据建立，这两个受体片段具有相似的，低亲和力（解离常数在5- 10 mM的范围内）的P16病毒，在两个complex.ConclusionThe寡糖结合槽中看到的相互作用是互补的结合聚糖的形状，但有相对较少的聚糖和蛋白质之间的氢键。因此，糖苷键的性质似乎是特异性的主要决定因素，而不是特定羟基的位置。低受体亲和力对于避免病毒释放被感染细胞的表面受体上的滞留抑制可能是重要的。有证据表明，致病性更强的菌株可能具有更弱的亲和力。
Background:Murine polyomavirus recognizes (α2,3)-linkedα-5-N-acetylneuraminic acid (sialic acid) on the surface of susceptible cells. While all strains bind to straight-chain receptors terminating in (α2,3)-linked sialic acid, some strains also bind to branched oligosaccharides that carry a second, (α2,6)-linked sialic acid. The ability to bind to these branched-chain receptors correlates with a single amino acid mutation at position 91 on the outer surface of the major capsid protein, VP1, and with a significant decrease in tumorigenicity.ResultsWe have determined the structures of polyomavirus strain P16, which bears a glycine at position 91, in complex with model compounds for both straight-chain and branched-chain sialoglycoconjugates. The structures have been refined to a resolution of 3.65 å. The ligands bind to a shallow groove on the surface of VP1. The sialic acid-(α2,3)-galactose moiety, which is common to both compounds, has specific and identical contacts. The additional (α2,6)-linked sialic acid moiety of the branched-chain receptor fragment fits into a surface pocket, but it has high thermal factors and does not form hydrogen bonds to groups on VP1. Data collected from crystals soaked at different oligosaccharide concentrations establish that both receptor fragments have similar, low affinities (dissociation constants in the range 5–10mM) for the P16 virus, consistent with the interactions seen in the two complexes.ConclusionThe oligosaccharide-binding groove is complementary to the shape of the bound glycan, but there are relatively few hydrogen bonds between glycan and protein. Thus, the nature of the glycosidic linkages appears to be the principal determinant of specificity, rather than the position of particular hydroxyl groups. The low receptor affinity may be important for avoiding inhibition of viral release by retention on surface receptors of infected cells. Evidence suggests that strains with still greater pathogenicity are likely to have even weaker affinity.