NS4A-2K-NS4B precursor, Dengue virus (NS4A-2K-NS4B)

The NS4A-2K-NS4B precursor is a cleavage intermediate in Dengue virus nonstructural polyprotein processing, linking the integral membrane proteins NS4A and NS4B via a 23-residue 2K fragment that serves as a signal sequence for NS4B translocation to the ER lumen.[1][4] This precursor specifically interacts with Dengue virus NS1 protein through residues in NS1's Wing connector domain (e.g., G161 and W168), a binding essential for RNA replication and biogenesis of ER-derived viral replication organelles, but not required for vesicle packet formation independent of replication.[4][5] NS4A within the complex oligomerizes on curved ER membranes, anchors replication sites via host vimentin interactions, and induces membrane reshaping into vesicles and double-membrane structures, while NS4B contributes to replication complex recruitment and host immune antagonism.[1][2][3] The interaction between NS4A (residues 40-76, including transmembrane helix) and NS4B (residues 84-146) stabilizes the complex with high affinity (Kd ~50 nM), and mutations disrupting these contacts impair viral replication.[2] As part of Dengue virus replication machinery, targeting NS4A-2K-NS4B or its NS1 interaction offers potential antiviral strategies, though no clinical drugs are reported.[2][3][4] Conservation across DENV serotypes supports broad-spectrum inhibitor potential, but low homology to other flaviviruses complicates pan-flaviviral development.[3]

Other names

NS4A-2K-4B cleavage intermediateNS4A-2K-4B precursor