Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

To obtain high resolution insights into the dynamic behaviors, we have performed 100- (Fig. 4E) , the Zika NS2B Cterminal residues lose the close contacts with its NS3pro domain and become highly exposed to bulk solvent only after 10 ns. This is completely consistent with NMR HSQC spectrum of 15 N-labeled Zika NS2B in complex with unlabeled NS3pro (Fig. 2C) , indicating that at least half of the Zika NS2B residues are highly dynamic. This unusually high dynamics appear to result mainly from the large sequence difference over the NS2B C-terminal residues 91-96 between Zika and Dengue (Fig. 5D) . Indeed, a short Zika NS2B with residues 75-100 deleted is sufficient to form a complex with its NS3pro, which has the less disordered structure but is enzymatically inactive, thus not only confirming that the Zika NS2B C-terminal residues is highly disordered, but also supporting the previous proposal that the formation of the closed conformation is essential for the enzymatic catalysis.