Two distinct protein-protein interfaces drive cooperative binding of the herpes simplex virus protein ICP8 to ssDNA, filament formation and annealing essential for viral replication.

ABSTRACT: Herpes simplex virus (HSV) replicates by forming DNA concatemers using a single strand annealing mechanism mediated by the multifunctional HSV protein ICP8. ICP8 binds cooperatively to form nucleoprotein filaments on ssDNA and promotes annealing of complementary single strands. These functions are believed to be mediated by ICP8:ICP8 protein-protein interactions (PPIs) between the flexible C-terminal domain of ICP8 and the N-terminal domain of a second ICP8 monomer. We previously presented genetic evidence for an ICP8:ICP8 PPI hotspot between two hydrophobic regions and showed that it is essential for the cooperative binding of ICP8 to ssDNA, ICP8 filament formation in vitro, and viral replication. This involves interactions between F1142, N1143, and F1144 (FNF) in the C terminal disordere

SUBMITTER: Discipio KA 

PROVIDER: S-EPMC12409425 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature