Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus
Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus
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DOI：
10.1073/pnas.1211037109
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发表时间：
2012-11-13
影响因子：
11.1
通讯作者：
Gao, George F.
中科院分区：
文献类型：
--
作者：
Li, Qing;Sun, Xiaoman;Gao, George F.
最近在蝙蝠中发现了流感病毒H17 N10的独特基因组，这对甲型流感病毒的起源和进化提出了相当大的疑问。它还鉴定了一种神经氨酸酶（NA）样蛋白N10，该蛋白与其他九种已确定的甲型流感NA血清型（N1-N9）高度不同。流感病毒NAs的结构解析和功能表征说明了NA结构的复杂性，从而提出了一个关键问题，即N10是否具有特殊的结构和功能。在这里，以2.20埃的分辨率解析了源自流感病毒A/小黄肩蝙蝠/Guatemala/153/2009（H17 N10）的N10晶体结构。总体而言，发现N10的结构与其他已知流感NA结构相似。体外酶促测定表明，N10缺乏典型的NA活性。一个详细的结构分析揭示了保守的活性位点残基的显着改变，是不利于结合和切割的末端连接的唾液酸受体。此外，观察到不寻常的150环（残基147-152）参与N10四聚体的相邻N10分子之间的分子间极性相互作用。我们对流感N10的研究提供了对唾液酸酶超家族的结构和功能的深入了解，并揭示了蝙蝠流感病毒感染的分子机制。
The recent discovery of the unique genome of influenza virus H17N10 in bats raises considerable doubt about the origin and evolution of influenza A viruses. It also identifies a neuraminidase (NA)-like protein, N10, that is highly divergent from the nine other well-established serotypes of influenza A NA(N1-N9). The structural elucidation and functional characterization of influenza NAs have illustrated the complexity of NA structures, thus raising a key question as to whether N10 has a special structure and function. Here the crystal structure of N10, derived from influenza virus A/little yellow-shouldered bat/Guatemala/153/2009 (H17N10), was solved at a resolution of 2.20 angstrom. Overall, the structure of N10 was found to be similar to that of the other known influenza NA structures. In vitro enzymatic assays demonstrated that N10 lacks canonical NA activity. A detailed structural analysis revealed dramatic alterations of the conserved active site residues that are unfavorable for the binding and cleavage of terminally linked sialic acid receptors. Furthermore, an unusual 150-loop (residues 147-152) was observed to participate in the intermolecular polar interactions between adjacent N10 molecules of the N10 tetramer. Our study of influenza N10 provides insight into the structure and function of the sialidase superfamily and sheds light on the molecular mechanism of bat influenza virus infection.