Helicase: Difference between revisions
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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 sequence|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. |
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 sequence|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. |
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==Superfamilies== |
==Superfamilies== |
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Revision as of 19:39, 26 October 2010
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.
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 of its 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.
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. scott owen is silly
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.
RNA Helicases
RNA Helicases fall into Super Families I and II, the rest belonging to DNA Helicases. Counter-intuitively, not all RNA Helicases exhibit helicase activity as defined by enzymatic function, i.e. proteins of the Swi/Snf family. Although these proteins carry the typical helicase motifs, hydrolize ATP in a nucleic acid dependent manner, and are built around a helicase core, generally no unwinding activity is observed.[5]
RNA Helicases that do exhibit unwinding activity have been characterized by at least two different mechanisms: canonical duplex unwinding, and local strand separation. Canonical duplex unwinding is the stepwise directional separation of a duplex strand as described above for DNA unwinding. However, local strand separation occurs by a process where the helicase enzyme is loaded at any place along the duplex. This is usually aided by a single stranded region of the RNA, and the loading of the enzyme is accompanied with ATP binding[6]. Once the helicase and ATP are bound local strand separation occurs, which requires binding of ATP but not the actual process of ATP hydrolysis[7]. Presented with fewer base pairs the duplex then dissociates without further assistance from the enzyme. This mode of unwinding is used by DEAD-box helicases.[8]
References
- ^ Lionnet T, Spiering MM, Benkovic SJ, Bensimon D, Croquette V (2007). "Real-time observation of bacteriophage T4 gp41 helicase reveals an unwinding mechanism". PNAS. 104 (50): 19790–19795. doi:10.1073/pnas.0709793104. PMC 2148377. PMID 18077411.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Johnson DS, Bai L, Smith BY, Patel SS, Wang MD (2007). "Single-molecule studies reveal dynamics of DNA unwinding by the ring-shaped t7 helicase". Cell. 129 (7): 1299–309. doi:10.1016/j.cell.2007.04.038. PMC 2699903. PMID 17604719.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b "Researchers solve mystery of how DNA strands separate". 2007-07-03. Retrieved 2007-07-05.
- ^ Dumont S, Cheng W, Serebrov V, Beran RK, Tinoco Jr I, Pylr AM, Bustamante C, "RNA Translocation and Unwinding Mechanism of HCV NS3 Helicase and its Coordination by ATP", Nature. 2006 Jan 5; 439: 105-108.
- ^ Trends Biochem Sci. 2010 Aug 31. RNA helicases at work: binding and rearranging. Jankowsky E. Center for RNA Molecular Biology & Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
- ^ Yang et al., DEAD-box proteins unwind duplexes by local strand separation, Mol. Cell 28 (2007), pp. 253–263
- ^ . Liu et al., ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding, Proc. Natl. Acad. Sci. U. S. A. 105 (2008), pp. 20209–20214
- ^ Jarmoskaite, I. and Russell, R., (2010) DEAD-box proteins as RNA helicases and chaperones. WIREs: RNA, in press.
External links
- DNA+Helicases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- RNA+Helicases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)