Investigating the folding dynamics of NS2B protein of Zika virus

Abstract

AbstractNS2B protein of the Zika virus acts as a co-factor for NS3 protease where only the cytosolic domain of NS2B is sufficient for the protease activity. At the same time, NS2B also involves in remodeling the NS3 protease structure. In isolation, we previously proved the NS2B cytosolic domain (residues 49-95) as a disordered type peptide conformation. Further, this study investigated the overall dynamics of NS2B full-length protein. Our Alphafold2 structure modeling system revealed surprising similarities between selected flavivirus NS2B proteins. This similarity reflects that the NS2B protein across flavivirus is conserved fold-wise. The MD simulation of Zika virus NS2B full-length protein shows that the cytosolic domain as a part of full-length protein is a disorder region supporting our previous experimental finding, which suggests the disordered nature of the cytosolic domain in isolation. Since the cytosolic domain of NS2B is essential for protease activity, we have also investigated the folding and dynamics of the NS2B cytosolic domain (residues 49-95) that shows the disorder to alpha helix transition in TFE. On the other hand, in the presence of SDS, macromolecular crowder like ficoll and PEG do not induce secondary structural change. This dynamics study could have implications for some unknown folds of the NS2B protein.