Structure and operating principles of a monkeypox virus replisome

TL;DR - This Nature study describes the structure and activation mechanism of the monkeypox virus replisome. It reveals how assembly-driven conformational changes in the E5 helicase–primase enable interactions that activate viral DNA replication machinery.

• The helicase–primase E5 forms a hexamer within the monkeypox virus replisome.
• Replisome assembly triggers large-scale conformational changes in E5.
• Two E5 primase domains contact the F8 polymerase thumb domain and the A22 subunit.
• These interactions activate the helicase–primase, clarifying a key operating principle of poxvirus replication.