NS4A and NS4B proteins from dengue virus: membranotropic regions

Proteins NS4A and NS4B from Dengue Virus (DENV) are highly hydrophobic transmembrane proteins which are responsible, at least in part, for the membrane arrangements leading to the formation of the viral replication complex, essential for the viral life cycle. In this work we have identified the membranotropic regions of DENV NS4A and NS4B proteins by performing an exhaustive study of membrane rupture induced by NS4A and NS4B peptide libraries on simple and complex model membranes as well as their ability to modulate the phospholipid phase transitions P(β')-L(α) of DMPC and L(β)-L(α)/L(α)-H(II) of DEPE. Protein NS4A presents three membrane active regions coincident with putative transmembrane segments, whereas NS4B presented up to nine membrane active regions, four of them presumably putative transmembrane segments. These data recognize the existence of different membrane-active segments on these proteins and support their role in the formation of the replication complex and therefore directly implicated in the DENV life cycle.