Movies of DNA translocation in the E1 replicative hexameric helicase

Eric Enemark & Leemor Joshua-Tor

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

The E1 protein of papillomavirus is a hexameric ring helicase and crystal structures show the E1 hexamer with single-stranded DNA discretely bound within the hexamer channel and nucleotides at the subunit interfaces. This structure demonstrates that only one strand of DNA passes through the hexamer channel and that the DNA-binding hairpins of each subunit form a spiral 'staircase' that sequentially tracks the oligonucleotide backbone. Consecutively grouped ATP, ADP and apo configurations correlate with the height of the hairpin, suggesting a straightforward DNA translocation mechanism. Each subunit sequentially progresses through ATP, ADP and apo states while the associated DNA-binding hairpin travels from the top staircase position to the bottom, escorting one nucleotide of single-stranded DNA through the channel. These events permute sequentially around the ring from one subunit to the next.

Adapted from Nature 442, 270-275 (2006)