Structural and mechanistic insights into the herpes simplex virus type 1 helicase-primase primosome.

ABSTRACT: DNA unwinding and primer synthesis are fundamental processes in genome replication. The human herpes simplex virus type 1 (HSV-1) helicase-primase forms a unique heterotrimeric primosome that is essential for viral DNA unwinding and primer synthesis and represents an ideal drug target. However, its molecular mechanism remains poorly understood. Here we report the cryo-electron microscopic structure of the primosome in complex with single-stranded DNA, ADP and Mg²⁺ to 3.47 Å resolution, which reveals that the primosome forms an unprecedented architecture in a fully open DNA binding groove between the helicase domains 1A and 2A-2B and that the primase subunit UL52 interacts extensively with the helicase subunit UL5 and accessory protein subunit UL8. Integrating mutagenesis, bioche

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12695949 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature