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 NEPH1N1 by phage display. When complexed with αRepE4, we were able to crystallize full-length NEPH1N1, and characterize the NEP-αRepE4 interface using an integrative native MS-XL-MS strategy, revealing a folded and monomeric NEP conformation. The N- and C-termini of NEPH1N1 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 αRepE4 and NEP. Similarly, we found that αRepE4 also binds NEP from human-isolated avian H7N9 and bovine-isolated avian H5N1 influenza viruses. Owing to their high degree of conservation, αRepE4 likely has the capacity to interact with NEP from numerous influenza A virus strains. Indeed, this, combined with the nanomolar affinity measured between NEP/αRepE4 could be explored further as a broad-range therapeutic strategy and/or a tool in cellulo to understand NEP function.