9T1M

Nuclear export protein/Non-structural protein 2 (NEP/NS2) in complex with artificial alpha Rep protein

9T1M の概要

• エントリーDOI: 10.2210/pdb9t1m/pdb
• 分子名称: Alpha Rep E4, Nuclear export protein (3 entities in total)
• 機能のキーワード: nuclear export protein, non-structural protein 2, influenza virus, synthetic protein, viral protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71053.89

構造登録者

Stelfox, A.J.,Ballandras-Colas, A.,Crepin, T. (登録日: 2025-10-21, 公開日: 2025-11-12, 最終更新日: 2025-11-19)

主引用文献

Stelfox, A.J.,Bessonne, M.,Bourhis, J.M.,Erba, E.B.,Albanese, P.,Compte, D.P.,Nevers, Q.,Urvoas, A.,Valerio-Lepiniec, M.,Minard, P.,Ruigrok, R.W.H.,Crepin, T.,Delmas, B.,Ballandras-Colas, A.
Monomeric Structure of Influenza A Virus NEP/NS2 Obtained With an Artificial Protein Highlights Conformational Plasticity.
J.Mol.Biol., 437:169511-169511, 2025

PubMed Abstract: The influenza virus nuclear export protein (NEP)/non-structural protein 2 (NS2) is a multifunctional protein, involved in viral ribonucleoprotein export from the nucleus, genome replication enhancement, and the adaption of avian influenza to mammals. Despite the growing attention on the importance of NEP in the influenza virus lifecycle and in interspecies transmission, the molecular details of how it performs its various roles are still not fully understood. For the purpose of assisting in structural characterization, a panel of artificial proteins (αReps) were selected against influenza virus A NEP by phage display. When complexed with E4, we were able to crystallize full-length NEP, and characterize the NEP-E4 interface using an integrative native MS-XL-MS strategy, revealing a folded and monomeric NEP conformation. The N- and C-termini of NEP pack together, with the middle linker region resembling a hinge, contrasting a previous structure where NEP is dimeric and elongated. Together these structures demonstrate the plasticity of NEP, a trait which may potentially aid NEP in binding cellular and viral partners. Using isothermal titration calorimetry (ITC) we measured a nanomolar interaction between E4 and NEP. Similarly, we found that E4 also binds NEP from human-isolated avian H7N9 and bovine-isolated avian H5N1 influenza viruses. Owing to their high degree of conservation, E4 likely has the capacity to interact with NEP from numerous influenza A virus strains. Indeed, this, combined with the nanomolar affinity measured between NEP/E4 could be explored further as a broad-range therapeutic strategy and/or a tool in cellulo to understand NEP function.

PubMed: 41175965
DOI: 10.1016/j.jmb.2025.169511

実験手法

X-RAY DIFFRACTION (2.33 Å)