Structural basis for Glycan-receptor binding by mumps virus hemagglutinin-neuraminidase
Structural basis for Glycan-receptor binding by mumps virus hemagglutinin-neuraminidase
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DOI：
10.1038/s41598-020-58559-6
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发表时间：
2020-01-31
影响因子：
4.6
通讯作者：
Silipo, Alba
中科院分区：
文献类型：
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作者：
Forgione, Rosa Ester;Di Carluccio, Cristina;Silipo, Alba
腮腺炎病毒是人类，特别是儿童呼吸道疾病的主要原因之一。在病毒表面糖蛋白中，血凝素-神经氨酸酶MuV-HN在病毒进入宿主细胞和感染性中起关键作用，因此代表了用于设计新型抑制剂的理想靶标。在这里，我们报告的病毒糖蛋白MuV-HN的宿主细胞表面唾液酸化聚糖的分子识别的详细分析。结合NMR、分子对接、分子模拟和CORCEMA-ST等技术，揭示了sialoglycans/MuV-HN复合物的结构特征。一个不同的酶活性对较长的和复杂的底物相比，无分支的配体的证据也检查了一个准确的NMR动力学分析。我们的研究结果为基于结构设计有效的抗腮腺炎药物提供了基础。
Mumps virus is one of the main cause of respiratory illnesses in humans, especially children. Among the viral surface glycoproteins, the hemagglutinin - neuraminidase, MuV-HN, plays key roles in virus entry into host cells and infectivity, thus representing an ideal target for the design of novel inhibitors. Here we report the detailed analysis of the molecular recognition of host cell surface sialylated glycans by the viral glycoprotein MuV-HN. By a combined use of NMR, docking, molecular modelling and CORCEMA-ST, the structural features of sialoglycans/MuV-HN complexes were revealed. Evidence for a different enzyme activity toward longer and complex substrates compared to unbranched ligands was also examined by an accurate NMR kinetic analysis. Our results provide the basis for the structure-based design of effective drugs against mumps-induced diseases.