**1. Introduction**

Many biologically functional protein regions do not fold spontaneously. This class of proteins, termed intrinsically disordered proteins (IDP), contains intrinsically disordered regions (IDR) which are devoid of stable secondary and tertiary structures under physiological conditions and rather, exist as dynamic ensembles of inter-converting conformers [1]. Many of these proteins gain a stable 3D structure only when they interact with their target molecules [2]. The ability to exert specific biological functions and to interact with various partners in spite of the lack of a precise 3D scaffold, challenges the classic paradigm according to which specificity can only be achieved through surface complementation between structured and conserved domains. It is now well accepted that intrinsic disorder is involved in a large spectrum of functional properties modulated through multi-partnership interactions with proteins and nucleic acids. With between 7.3% and 77% of residues being disordered, the proteome of viruses on the whole presents the highest variability of intrinsic disorder in the living world [3–5]. The genus *Potyvirus* represents one of the largest and most economically damaging genus of plant-infecting viruses [6]. These viruses possess a single-stranded, polyadenylated, positive-sense

genomic RNA which is covalently linked at its 5 end to a viral protein, the viral protein genome-linked (VPg) [7,8]. The VPgs from several potyviruses, namely lettuce mosaic virus (LMV) [9], potato virus Y (PVY) [10], and Potato virus A (PVA) [11] have been experimentally characterized as intrinsically disordered. The potyviral VPg has been shown to interact with several viral and host factors. It is assumed to be a multifunctional protein involved in essential steps of the virus infectious cycle, translation, replication, and movement [12,13]. The VPg recruits the host eukaryotic translation initiation factor 4E (eIF4E), or its isoform eIF(iso)4E, in an interaction that is crucial for virus infection [14–16]. Mutations in the central region of VPg (residues 80–125) are associated with host resistance breakdown, [17–19]. In the LMV VPg, this central region interacts with eIF4E [20]. This region has been predicted to be an IDR for VPg from twelve potyviral species [9,21]. The study reported here analyzes the contribution of VPg and eIF4E flexible regions to the hydrodynamic properties of the two proteins, either monomeric, or associated in a binary complex.
