Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France; EMBL Grenoble Outstation, 71 Avenue des Martyrs, BP181, F-38042 Grenoble Cedex 9, France.
Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
J Mol Biol. 2020 May 1;432(10):3353-3359. doi: 10.1016/j.jmb.2020.03.021. Epub 2020 Mar 25.
Here, we describe the crystal structures of two distinct isoforms of ligand-free human karyopherin RanBP5 and investigate its global propensity to interact with influenza A virus polymerase. Our results confirm the general architecture and mechanism of the IMB3 karyopherin-β subfamily whilst also highlighting differences with the yeast orthologue Kap121p. Moreover, our results provide insight into the structural flexibility of β-importins in the unbound state. Based on docking of a nuclear localisation sequence, point mutations were designed, which suppress influenza PA-PB1 subcomplex binding to RanBP5 in a binary protein complementation assay.
在这里，我们描述了两种不同的无配体人核孔蛋白 RanBP5 同型物的晶体结构，并研究了其与甲型流感病毒聚合酶相互作用的整体倾向。我们的结果证实了 IMB3 核孔蛋白-β亚家族的一般结构和机制，同时也突出了与酵母同源物 Kap121p 的差异。此外，我们的结果还提供了关于未结合状态下β-importin 结构灵活性的见解。基于核定位序列的对接，设计了点突变，这些突变在二元蛋白互补测定中抑制了流感 PA-PB1 亚基复合物与 RanBP5 的结合。
