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Secondary structure and membrane topology of dengue virus NS4A protein in micelles

机译:胶束登革热病毒NS4A蛋白的二级结构和膜拓扑

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摘要

Abstract Dengue virus (DENV) non-structural (NS) 4A is a membrane protein essential for viral replication. The N-terminal region of NS4A contains several helices interacting with the cell membrane and the C-terminal region consists of three potential transmembrane regions. The secondary structure of the intact NS4A is not known as the previous structural studies were carried out on its fragments. In this study, we purified the full-length NS4A of DENV serotype 4 into dodecylphosphocholine (DPC) micelles. Solution NMR studies reveal that NS4A contains six helices in DPC micelles. The N-terminal three helices are amphipathic and interact with the membrane. The C-terminal three helices are embedded in micelles. Our results suggest that NS4A contains three transmembrane helices. Our studies provide for the first time structural information of the intact NS4A of DENV and will be useful for further understanding its role in viral replication. Graphical abstract Display Omitted Highlights ? Full length dengue NS4A was produced for structural studies. ? Backbone resonance assignment for NS4A in micelles was obtained. ? NS4A contains six helices. ? The C-terminal three helices are transmembrane helices.
机译:摘要登革病毒(DENV)非结构(NS)4A是膜蛋白,对病毒复制是必不可少的。 NS4A的N-末端区域含有几个与细胞膜相互作用的螺旋,并且C末端区域由三个势跨膜区域组成。完整NS4a的二级结构不称为先前的结构研究在其碎片上进行。在这项研究中,我们将DenV血清型4的全长NS4A纯化成十二烷基磷胆碱(DPC)胶束。解决方案NMR研究表明,NS4A在DPC胶束中含有六个螺旋。 n末端三个螺旋是两亲性的并且与膜相互作用。 C末端三个螺旋嵌入胶束中。我们的结果表明,NS4A包含三个跨膜螺旋。我们的研究提供了丹佛的完整NS4A的第一次结构信息,并将有助于进一步了解其在病毒复制中的作用。图形抽象显示省略了亮点?为结构研究制作全长登革热NS4A。还获得胶束中NS4A的骨干共振分配。还NS4A包含六个螺旋。还C终端三螺旋是跨膜螺旋。

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