PROSITE documentation PDOC51206

Superfamily 3 helicase domain profile

Helicases have been classified in 5 superfamilies (SF1-SF5) [1]. All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) (see <PDOC00017>) and Walker B (Mg2+-binding aspartic acid) motifs [1]. Superfamily 3 consists of helicases encoded mainly by small RNA and DNA viruses and some large nucleocytoplasmic DNA viruses [2,3]. Small viruses are very dependent on the host-cell machinery to replicate. SF3 helicase in small DNA viruses is associated with an origin-binding domain. By pairing a domain that recognizes the ori with a helicase, the virus can bypass the host-cell-based regulation pathway and initiate its own replication. The protein binds to the viral ori leading to origin unwinding. Cellular replication proteins are then recruited to the ori and the viral DNA is replicated.

In SF3 helicases the Walker A and Walker B motifs are separated by spacers of rather uniform, and relatively short, lenght. In addition to the A and B motifs this family is caracterized by a third motif (C) which resides between the B motif and the C-terminus of the conserved region. This motif consists of an Asn residue preceded by a run of hydrophobic residues [4].

Several structure of SF3 helicases have been solved (see <PDB:1N25>) [5]. They all possess the same core α/β fold, consisting of a five-stranded parallel β sheet flanked on both sides by several α helices. In contrast to SF1 and SF2 helicases, which have RecA-like core folds, the strand connectivity within the α/β core domain is that of AAA+ proteins [6]. The SF3 helicase proteins assemble into a hexameric ring.

Some proteins known to contain an SF3 helicase domain are listed below:

• Polyomavirus large T antigen. It initiates DNA unwinding and replication via interactions with the viral origin of replication.
• Papillomavirus E1 protein. An ATP-dependent DNA helicase required for initiation of viral DNA replication.
• Parvovirus Rep/NS1 protein, which is also required for the initiation of viral replication.
• Poxviridae and other large DNA viruses D5 protein.
• Bacteriophage DNA primase/helicase protein.
• Bacterial prophage DNA primase/helicase protein.
• ssRNA positive strand viruses RNA1 polyprotein.

To recognize this domain we have developed two profiles. The first one is directed against DNA viruses SF3 helicase and the second one is specific for ssRNA positive-strand viruses SF3 helicase.