5V5O

Structure of NLS2K of influenza A virus nucleoprotein bound to importin alpha

5V5O の概要

• エントリーDOI: 10.2210/pdb5v5o/pdb
• 関連するPDBエントリー: 4ZDU 5V5P
• 分子名称: Importin subunit alpha-1, Nucleoprotein (3 entities in total)
• 機能のキーワード: nuclear import, nls, viral protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 62591.88

構造登録者

Sankhala, R.S.,Lokareddy, R.K.,Cingolani, G. (登録日: 2017-03-14, 公開日: 2018-03-14, 最終更新日: 2023-10-04)

主引用文献

Wu, W.,Sankhala, R.S.,Florio, T.J.,Zhou, L.,Nguyen, N.L.T.,Lokareddy, R.K.,Cingolani, G.,Pante, N.
Synergy of two low-affinity NLSs determines the high avidity of influenza A virus nucleoprotein NP for human importin alpha isoforms.
Sci Rep, 7:11381-11381, 2017

PubMed Abstract: The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates with the minor NLS-pocket. Though peptides corresponding to NLS1 and NLS2 bind weakly to importin α, the two NLSs synergize in the context of the full length NP to confer high avidity for importin α7, explaining why the virus efficiently replicates in the respiratory tract that exhibits high levels of this isoform. This study, the first to functionally characterize NLS2, demonstrates NLS2 plays an important and unexpected role in influenza A virus infection. We propose NLS1 and NLS2 form a bipartite NLS in trans, which ensures high avidity for importin α7 while preventing non-specific binding to viral RNA.

PubMed: 28900157
DOI: 10.1038/s41598-017-11018-1

実験手法

X-RAY DIFFRACTION (2.243 Å)