Unwinding of a DNA replication fork by a hexameric viral helicase

Abstract Hexameric helicases are motor proteins that unwind double-stranded DNA (dsDNA) during replication but how they optimised for strand separation is unclear. Here we present the cryo-EM structure of full-length E1 helicase from papillomavirus, revealing all arms a bound fork and their interactions with helicase. The junction located at entrance to collar ring, sits above AAA + assembly. dsDNA escorted 5´ single-stranded (ssDNA) away unwinding point by origin binding domains. 3´ ssDNA interacts six spirally-arranged ?-hairpins cyclical top-to-bottom movement pulls through Pulling RF against ring separates base-pairs, while modelling conformational cycle suggest an accompanying has auxiliary role, helping make efficient use ATP in duplex unwinding.