Linear schematic of an E1 protein

E1 is the replication initiator protein. The replication origin contains specific consensus motifs for the E1 and E2 proteins, which initially cooperatively bind to the origin through sequence specific DNA binding domains. Next, E1 converts to a double hexameric helicase to unwind the viral DNA bidirectionally. The E1 protein shuttles between the nucleus and cytoplasm and this is regulated by phosphorylation of an N-terminal shuttling domain. E1 proteins are approximately 600 amino acids long and are encoded by all papillomaviruses. They consist of an N-terminal shuttling domain, an origin-specific DNA binding domain, an oligomerization region and a helicase domain.