Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties
Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties
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DOI：
10.1073/pnas.0808101106
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发表时间：
2009-03-10
影响因子：
11.1
通讯作者：
Stubbs, Milton T.
中科院分区：
文献类型：
--
作者：
Neumann, Piotr;Lieber, Diana;Stubbs, Milton T.
博尔纳病病毒（Borna disease virus，BDV）是一种嗜神经性包膜RNA病毒，可引起哺乳动物中枢神经系统的持续性非细胞溶解性感染。BDV属于单负链RNA病毒目，其还包括负链RNA病毒（NSV）埃博拉病毒、马尔堡病毒、水疱性口炎病毒、狂犬病病毒、腮腺炎病毒和麻疹病毒。BDV-M是BDV的基质蛋白（M蛋白），是NSV中最小的M蛋白（16.2kDa）。M蛋白在病毒组装和出芽中起关键作用，介导病毒衣壳、包膜和糖蛋白刺突之间的相互作用，并且因此负责病毒颗粒的结构稳定性和个体形式。在这里，我们报告了BDV-M的三维结构，BDV-M是来自非节段RNA NSV的全长M蛋白结构。BDV-M单体表现出与埃博拉M蛋白（VP 40）的N-末端结构域的结构相似性，而四聚体的表面电荷提供了BDV-M的膜缔合的线索。晶体中额外的电子密度揭示了结合核酸的存在，解释为胞苷-5 '-单磷酸。异源表达的BDV-M与从表达宿主摄取的中值长度为16 nt的ssRNA寡核苷酸共纯化并保护所述ssRNA寡核苷酸。本文呈现的结果表明，BDV-M将能够同时结合RNA和脂质膜，从而扩展M蛋白功能的库。
Borna disease virus (BDV) is a neurotropic enveloped RNA virus that causes a noncytolytic, persistent infection of the central nervous system in mammals. BDV belongs to the order Mononegavirales, which also includes the negative-strand RNA viruses (NSVs) Ebola, Marburg, vesicular stomatitis, rabies, mumps, and measles. BDV-M, the matrix protein (M-protein) of BDV, is the smallest M-protein (16.2 kDa) among the NSVs. M-proteins play a critical role in virus assembly and budding, mediating the interaction between the viral capsid, envelope, and glycoprotein spikes, and are as such responsible for the structural stability and individual form of virus particles. Here, we report the 3D structure of BDV-M, a full-length M-protein structure from a nonsegmented RNA NSV. The BDV-M monomer exhibits structural similarity to the N-terminal domain of the Ebola M-protein (VP40), while the surface charge of the tetramer provides clues to the membrane association of BDV- M. Additional electron density in the crystal reveals the presence of bound nucleic acid, interpreted as cytidine-5'-monophosphate. The heterologously expressed BDV-M copurifies with and protects ssRNA oligonucleotides of a median length of 16 nt taken up from the expression host. The results presented here show that BDV- M would be able to bind RNA and lipid membranes simultaneously, expanding the repertoire of M-protein functionalities.