Papillomavirus E1 hexameric helicase
Bovine papillomavirus type I
Papilomavirus is a virus which parasites in bovines and induces the knot on the skin known as “pappiloma”. Papilomavirus has circular double-strand DNA (dsDNA) as a genomic substrate. When DNA replication initiates, the dsDNA of viruses is unwired to the single-stranded DNA(ssDNA) like that of prokaryotes and eucaryotes. Herein described is a DNA helicase of bovine pallilomavirus, E1 protein, that catalyzes the dsDNA unwiring. Surprisingly, E1 protein can bind to dsDNA and starts the unwiring as well as Tag of SV40 virus (PDB: 1SVM) does while many DNA helicases of prokaryotes and eucaryotes binds to where DNA has been already unwired. The trick of this property has been considered to be in the ring structure of E1 protein.
E1 protein of pappilomavirus forms ring structure which contains six subunits located rotationally symmetrically(fig.1). The diameter of the ring is not larger than that of that of double-stranded DNA, so the ring can permeate only single-stranded DNA. Each subunit of E1 protein protrudes “hairpin structure”, which binds to the nucleotide backbone with cationic amino acid residues (K506 and H507), to the center of the ring. The six hairpins line like spiral staircase that sequentially tracks the nucleotide of single-stranded DNA. The hairpin height changes depending on adenine nucleotide binding states in the inter-domain region of E1 protein; ATP, ADP and apo states. This conformational change in the ring of E1 protein induces permeation of single-stranded DNA through the ring.
Fig.1 Molecular complex of a ssDNA and six E1 proteins; red: ssDNA, orange,yellow,green,blue,deepblue and purple: E1 protein
Protein Data Bank (PDB)
Enemark, E.J. Joshua-Tor, L.; "Mechanism of DNA translocation in a replicative hexameric helicase"; Nature; (2006) 442:270-275.
author: Daisuke Ino