Identification of a Novel Regulatory Sequence of Actin Nucleation Promoting Factor Encoded by Autographa californica Multiple Nucleopolyhedrovirus*
Identification of a Novel Regulatory Sequence of Actin Nucleation Promoting Factor Encoded by Autographa californica Multiple Nucleopolyhedrovirus*
复制标题
DOI：
10.1074/jbc.m114.635441
复制
发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Yun Wang;Yongli Zhang;Shi Han;Xue Hu;Yuan Zhou;Jingfang Mu;R. Pei;Chunchen Wu;Xinwen Chen
中科院分区：
文献类型：
--
作者：
Yun Wang;Yongli Zhang;Shi Han;Xue Hu;Yuan Zhou;Jingfang Mu;R. Pei;Chunchen Wu;Xinwen Chen
背景：杆状病毒肌动蛋白成核促进因子（NPF）的调控机制尚不明确。结果：杆状病毒NPF在其N端含有一个多功能调控序列（MRS）。结论：杆状病毒NPF受宿主蛋白酶体和病毒核衣壳蛋白C42的n端mrs调控。意义：发现新的病毒NPF调控机制。成核促进因子（NPFs）诱导的肌动蛋白聚合是真核细胞最基本的生物过程之一。NPFs在C端附近含有一个保守输出结构域（VCA结构域），该结构域与细胞肌动蛋白相关蛋白2/3复合物（Arp2/3）相互作用并激活其诱导肌动蛋白聚合，在N端附近含有一个多样的调控结构域。加州自签名多核多角体病毒（AcMNPV）核衣壳蛋白P78/83是一种病毒编码的NPF，包含一个c端VCA结构域，并在病毒感染的细胞中诱导肌动蛋白聚合。然而，P78/83的N端与其他已鉴定的npf没有相似之处，这表明P78/83可能具有独特的调控机制。在这项研究中，我们确定了位于P78/83 N端附近的多功能调控序列（MRS），并确定其功能之一是作为降解子以蛋白酶体依赖的方式介导P78/83降解。在acmnpv感染的细胞中，MRS还与另一种核衣壳蛋白BV/ODV-C42结合，稳定P78/83并调节P78/83- arp2 /3相互作用，以协调肌动蛋白聚合。此外，MRS对于P78/83进入核衣壳也是必不可少的，以确保P78/83诱导的肌动蛋白聚合为病毒粒子的迁移提供动力。MRS的三重功能使P78/83在AcMNPV复制周期中成为必需的病毒蛋白，并讨论了MRS在协调病毒诱导的肌动蛋白聚合和病毒基因组脱壳中的可能作用。
Background: The regulatory mechanism of baculoviral actin nucleation promoting factor (NPF) remains elusive. Results: Baculoviral NPF harbors a multifunctional regulatory sequence (MRS) at its N terminus. Conclusion: Baculoviral NPF is modulated by the host proteasome and viral nucleocapsid protein C42 through its N-terminal MRS. Significance: Identification of a novel regulatory mechanism of viral NPF. Actin polymerization induced by nucleation promoting factors (NPFs) is one of the most fundamental biological processes in eukaryotic cells. NPFs contain a conserved output domain (VCA domain) near the C terminus, which interacts with and activates the cellular actin-related protein 2/3 complex (Arp2/3) to induce actin polymerization and a diverse regulatory domain near the N terminus. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) nucleocapsid protein P78/83 is a virus-encoded NPF that contains a C-terminal VCA domain and induces actin polymerization in virus-infected cells. However, there is no similarity between the N terminus of P78/83 and that of other identified NPFs, suggesting that P78/83 may possess a unique regulatory mechanism. In this study, we identified a multifunctional regulatory sequence (MRS) located near the N terminus of P78/83 and determined that one of its functions is to serve as a degron to mediate P78/83 degradation in a proteasome-dependent manner. In AcMNPV-infected cells, the MRS also binds to another nucleocapsid protein, BV/ODV-C42, which stabilizes P78/83 and modulates the P78/83-Arp2/3 interaction to orchestrate actin polymerization. In addition, the MRS is also essential for the incorporation of P78/83 into the nucleocapsid, ensuring virion mobility powered by P78/83-induced actin polymerization. The triple functions of the MRS enable P78/83 to serve as an essential viral protein in the AcMNPV replication cycle, and the possible roles of the MRS in orchestrating the virus-induced actin polymerization and viral genome decapsidation are discussed.