Faculty of Advanced Life Science, Hokkaido University, Kita-10, Nishi-8, Kita-ku, Sapporo, 060-0810, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, 060-0812, Japan.
Biochem Biophys Res Commun. 2020 Aug 20;529(2):507-512. doi: 10.1016/j.bbrc.2020.05.195. Epub 2020 Jul 2.
Lyssavirus P protein is a multifunctional protein that interacts with numerous host-cell proteins. The C-terminal domain (CTD) of P is important for inhibition of JAK-STAT signaling enabling the virus to evade host immunity. Several regions on the surface of rabies virus P are reported to interact with host factors. Among them, an extended, discrete hydrophobic patch of P CTD is notable. Although structures of P CTD of two strains of rabies virus, and of mokola virus have been solved, the structure of P CTD for Duvenhage virus, which is functionally divergent from these species for immune evasion function, is not known. Here, we analyze the structures of P CTD of Duvenhage and of a distinct rabies virus strain to gain further insight on the nature and potential function of the hydrophobic surface. Molecular contacts in crystals suggest that the hydrophobic patch is important to intermolecular interactions with other proteins, which differ between the lyssavirus species.
狂犬病病毒 P 蛋白是一种多功能蛋白，可与许多宿主细胞蛋白相互作用。P 的 C 末端结构域（CTD）对于抑制 JAK-STAT 信号通路很重要，使病毒能够逃避宿主免疫。已报道狂犬病病毒 P 表面的几个区域与宿主因子相互作用。其中，P CTD 的一个扩展的离散疏水面引人注目。尽管已解决了两种狂犬病病毒株和莫科拉病毒的 P CTD 结构，但功能上与这些物种不同的杜文哈格病毒的 P CTD 结构尚不清楚。在这里，我们分析了杜文哈格病毒和另一种独特的狂犬病病毒株的 P CTD 结构，以进一步了解疏水面的性质和潜在功能。晶体中的分子接触表明，疏水面对于与其他蛋白的分子间相互作用很重要，而这些相互作用在不同的弹状病毒种间存在差异。
