Structure of E. coli helicase RuvA

Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands (i.e. DNA, RNA, or RNA-DNA hybrid) using energy derived from ATP hydrolysis.

[edit] Function

Many cellular processes (DNA replication, transcription, translation, recombination, DNA repair, ribosome biogenesis) involve the separation of nucleic acid strands. Helicases are often utilized to separate strands of a DNA double helix or a self-annealed RNA molecule using the energy from ATP hydrolysis, a process characterized by the breaking of hydrogen bonds between annealed nucleotide bases. They move incrementally along one nucleic acid strand of the duplex with a directionality and processivity specific to each particular enzyme. There are many helicases (14 confirmed in E. coli, 24 in human cells) resulting from the great variety of processes in which strand separation must be catalyzed.^{[citation needed]}

Helicases adopt different structures and oligomerization states. Whereas DnaB-like helicases unwind DNA as donut shaped hexamers, other enzymes have been shown to be active as monomers or dimers. Studies have shown that helicases may act passively, waiting for uncatalyzed unwinding to take place and then translocating between displaced strands,^[1] or can play an active role in catalyzing strand separation using the energy generated in ATP hydrolysis.^[2] In the latter case, the helicase acts comparably to an active motor, unwinding and translocating along its substrate as a direct result ATPase activity.^[3]. Helicases may process much faster in vivo than in vitro due to the presence of accessory proteins that aid in the destabilization of the fork junction.^[3]

Defects in the gene that codes helicase cause Werner syndrome, a disorder characterized by the appearance of premature aging.

[edit] Structural features

The common function of helicases accounts for the fact that they display a certain degree of amino acid sequence homology; they all possess common sequence motifs located in the interior of their primary sequence. These are thought to be specifically involved in ATP binding, ATP hydrolysis and translocation on the nucleic acid substrate. The variable portion of the amino acid sequence is related to the specific features of each helicase.

Based on the presence of defined helicase motifs, it is possible to attribute a putative helicase activity to a given protein, though the presence of a motif does not confirm the protein as a helicase. Conserved motifs do, however, support an evolutionary homology among enzymes. Based on the presence and the form of helicase motifs, helicases have been separated in 4 superfamilies and 2 smaller families. Some members of these families are indicated, with the organism from which they are extracted, and their function.

[edit] Superfamilies

• Superfamily I: UvrD (E. coli, DNA repair), Rep (E. coli, DNA replication), PcrA (Staphylococcus aureus, recombination), Dda (bacteriophage T4, replication initiation), RecD (E. coli, recombinational repair), TraI (F-plasmid, conjugative DNA transfer).
• Superfamily II: RecQ (E. coli, DNA repair), eIF4A (Baker's Yeast, RNA translation), WRN (human, DNA repair), NS3^[4] (Hepatitis C virus, replication). TRCF (Mfd) (E.coli, transcription-repair coupling).
• Superfamily III: LTag (Simian Virus 40, replication), E1 (human papillomavirus, replication), Rep (Adeno-Associated Virus, replication, viral integration, virion packaging).
• DnaB-like family: dnaB (E. coli, replication), gp41 (bacteriophage T4, DNA replication),T7gp4 (bacteriophage T7, DNA replication).
• Rho-like family: Rho (E. coli, transcription termination).

Note that these superfamilies do not subsume all possible helicases. For example XPB and ERCC2 are helicases not included in any of the above families.

[edit] References

[edit] External links

• MeSH DNA+Helicases
• MeSH RNA+Helicases