Zika virus NS4A cytosolic region (residues 1-48) is an intrinsically disordered domain and folds upon binding to lipids.

In flaviviruses, the NS4A is an integral transmembrane protein that contributes to form virus-induced membrane curvature. However, structural features of NS4A are not documented in Zika virus, and it is one of the least characterized proteins. Thus, this work focused on investigating the secondary structural elements of the Zika virus NS4A, where we characterized the cytosolic region of protein NS4A (residues 1-48) under variable environmental conditions. We found NS4A (residues 1-48) as an intrinsically disordered domain that has an intrinsic ability to form helical fold in the presence of membranous environment, osmolyte, and fluoro alcohol. The conformational change in NS4A (residues 1-48) secondary structure upon interaction with lipid vesicles can be correlated with the disorder-function paradigm concept. This change in NS4A (residues 1-48) secondary structure may suggest its implication in membrane rearrangement and replication complex formation.