Mapping the domain of interaction of PVBV VPg with NIa-Pro: Role of N-terminal disordered region of VPg in the modulation of structure and function.

VPg-Pro is involved in polyprotein processing, therefore its regulation is important for a successful potyviral infection. We report here that the N-terminal disordered region of VPg forms the domain of interaction with NIa-Pro. This region is also demonstrated to be responsible for modulating the protease activity of VPg-Pro, both in cis and trans. The disordered nature of VPg is elicited by the N-terminal 22 residues as removal of these residues (∆N22 VPg) brought about gross structural and conformational changes in the protein. Interestingly, ∆N22 VPg gained ATPase activity which suggested the presence of autoinhibitory motif within the N-terminal region of VPg. The autoinhibition gets relieved upon interaction of VPg with NIa-Pro or removal of the inhibitory motif. Thus, the N-terminal 22 residues of VPg qualify as molecular recognition feature (MoRF), regulating both protease and ATPase activity of VPg-Pro as well as forming the domain of interaction with other viral/host proteins.