6E5U

Crystal structure of the mRNA export receptor NXF1/NXT1 in complex with influenza virus NS1 protein

6E5U の概要

• エントリーDOI: 10.2210/pdb6e5u/pdb
• 分子名称: Nuclear RNA export factor 1, NTF2-related export protein 1, Non-structural protein 1, ... (4 entities in total)
• 機能のキーワード: mrna nuclear export, rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 395809.83

構造登録者

Xie, Y.,Ren, Y. (登録日: 2018-07-23, 公開日: 2019-04-24, 最終更新日: 2023-10-11)

主引用文献

Zhang, K.,Xie, Y.,Munoz-Moreno, R.,Wang, J.,Zhang, L.,Esparza, M.,Garcia-Sastre, A.,Fontoura, B.M.A.,Ren, Y.
Structural basis for influenza virus NS1 protein block of mRNA nuclear export.
Nat Microbiol, 4:1671-1679, 2019

PubMed Abstract: Influenza viruses antagonize key immune defence mechanisms via the virulence factor non-structural protein 1 (NS1). A key mechanism of virulence by NS1 is blocking nuclear export of host messenger RNAs, including those encoding immune factors; however, the direct cellular target of NS1 and the mechanism of host mRNA export inhibition are not known. Here, we identify the target of NS1 as the mRNA export receptor complex, nuclear RNA export factor 1-nuclear transport factor 2-related export protein 1 (NXF1-NXT1), which is the principal receptor mediating docking and translocation of mRNAs through the nuclear pore complex via interactions with nucleoporins. We determined the crystal structure of NS1 in complex with NXF1-NXT1 at 3.8 Å resolution. The structure reveals that NS1 prevents binding of NXF1-NXT1 to nucleoporins, thereby inhibiting mRNA export through the nuclear pore complex into the cytoplasm for translation. We demonstrate that a mutant influenza virus deficient in binding NXF1-NXT1 does not block host mRNA export and is attenuated. This attenuation is marked by the release of mRNAs encoding immune factors from the nucleus. In sum, our study uncovers the molecular basis of a major nuclear function of influenza NS1 protein that causes potent blockage of host gene expression and contributes to inhibition of host immunity.

PubMed: 31263181
DOI: 10.1038/s41564-019-0482-x

実験手法

X-RAY DIFFRACTION (3.8 Å)