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Helicases are a class of enzymes vital to all living organisms. They are motor proteins that translocate unidirectionally along single-stranded nucleic acids using energy derived from nucleotide hydrolysis, often separating the two strands of a nucleic acid double helix in the process. (i.e. DNA, RNA, or RNA-DNA hybrid)
Function
Many cellular processes (DNA replication, RNA synthesis, RNA transcription, DNA recombination, DNA repair) involve separation of the nucleic acid strands. There are many helicases (14 identified so far in E. coli, 24 in human cells) resulting from the great variety of processes in which strand separation must be catalyzed. All helicases separate the strands of a double helix using the energy derived from ATP hydrolysis. They move along one strand with a directionnality specific to each enzyme (3'-5' or 5'-3') while separating the strands.
Structural Features
The common features shared by helicases account for the fact that they display amino acid sequence homology to a certain degree: they all possess common sequence motifs located in the central part of their sequence. These are thought to be specifically involved in ATP binding, ATP hydrolysis and translocation on the nucleic acid template. The variable part of the amino acid sequence is related to the specific features of each helicase. Based on the presence of the so-called helicase motifs, it is possible to attribute a putative helicase activity to a given protein. However, the presence of these motifs does not necessarily imply that the protein indeed possesses helicase activity. Based on the presence and the form of the 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.
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. Their precise mechanisms of action are still unclear.
Helicase Superfamilies
Superfamily I: UvrD (E. coli, DNA repair), Rep (E. coli, DNA replication), PcrA (Bacillus stearothermophilus, role not precisely known), Dda (bacteriophage T4, replication initiation).
Superfamily II: RecQ (E. coli, DNA repair), BLM (human, DNA repair), WRN (human, DNA repair), NS3 Dumont S, Cheng W, Serebrov V, Beran RK, Tinoco Jr. I, Pylr AM, Bustamante C, Translocation and Unwinding Mechanism of HCV NS3 Helicase and its Coordination by ATP", Nature. 2006 Jan 5; 439: 105-108. (Hepatitis C virus, replication).
Superfamily III: LTag (Simian Virus 40, replication), E1 (human papillomavirus, replication).
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 factor ).
References
- Bird L, Subramanya HS, Wigley DB, a unifying structural theme?", Current Opinion in Structural Biology. 1998 Feb; 8 (1): 14-18.
- Betterton MD, Julicher F, of nucleic-acid double strands by helicases: active versus passive opening.", Physical Review E. 2005 Jan; 71 (1): 011904.
"Helicase"