Helicase
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222658629
2008-06-30T13:56:03Z
Benbest
167797
/* Superfamilies */ others
[[Image:Helicase.png|thumb|220px|Structure of E. coli helicase RuvA]]
'''Helicases''' are a class of [[enzyme]]s vital to all living [[organism]]s. They are motor proteins that move directionally along a [[nucleic acid]] [[Phosphodiester bond|phosphodiester backbone]], separating two [[Annealing (biology)|annealed]] nucleic acid strands (i.e. [[DNA]], [[RNA]], or RNA-DNA hybrid) using energy derived from [[nucleotide]] [[hydrolysis]].
==Function==
Many cellular processes ([[DNA replication]], [[transcription]], [[translation (biology)|translation]], [[Genetic recombination|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 [[Adenosine triphosphate|ATP]] or [[Guanosine triphosphate|GTP]] hydrolysis, a process characterized by the breaking of [[hydrogen bond|hydrogen bonds]] between [[Base pair|annealed nucleotide bases]]. They move incrementally along one [[nucleic acid]] strand of the duplex with a [[Directionality (molecular biology)|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.{{Fact|date=February 2007}}
Helicases adopt different structures and [[oligomerization]] states. Whereas [[DnaB]]-like helicases unwind [[DNA]] as donut shaped [[hexamer]]s, other enzymes have been shown to be active as [[monomer]]s or [[dimer]]s. Recent studies showed that helicases do not merely wait passively for the [[Replication fork|fork]] to widen, but play an active role in forcing the fork to open,<ref name=Johnson>{{cite journal |author=Johnson DS, Bai L, Smith BY, Patel SS, Wang MD |title=Single-molecule studies reveal dynamics of DNA unwinding by the ring-shaped t7 helicase |journal=Cell |volume=129 |issue=7 |pages=1299–309 |year=2007 |pmid=17604719 |doi=10.1016/j.cell.2007.04.038}}</ref> thus it is an active motor unwinding its substrate<ref name=physorg1>{{cite web |url=http://www.physorg.com/news102663442.html |title=Researchers solve mystery of how DNA strands separate |date=[[2007-07-03]] |accessdate=2007-07-05}}</ref>. 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.<ref name=physorg1 />
==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 motif]]s located in the interior of their [[Primary structure|primary sequence]]. These are thought to be specifically involved in [[Adenosine triphosphate|ATP]] binding, [[Adenosine triphosphate|ATP]] [[hydrolysis]] and translocation on the [[nucleic acid]] [[Substrate (biochemistry)|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 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.
==Superfamilies==
*'''Superfamily I''': UvrD ([[E. coli]], DNA repair), Rep (E. coli, DNA replication), PcrA ([[Staphylococcus aureus]], recombination), Dda (bacteriophage T4, replication initiation).
*'''Superfamily II''': [[RecQ helicase|RecQ]] (E. coli, DNA repair), eIF4A ([[saccharomyces cerevisiae|Baker's Yeast]], RNA translation), [[WRN (gene)|WRN]] (human, DNA repair), NS3<ref> Dumont S, Cheng W, Serebrov V, Beran RK, Tinoco Jr I, Pylr AM, [[Carlos Bustamante|Bustamante C]], [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16397502&query_hl=3&itool=pubmed_DocSum|"RNA Translocation and Unwinding Mechanism of HCV NS3 Helicase and its Coordination by ATP"], [[Nature (journal)|Nature]]. 2006 Jan 5; 439: 105-108. </ref> ([[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 helicase|dnaB]] (E. coli, replication), gp41 ([[bacteriophage T4]], DNA replication),[[T7 DNA Helicase|T7gp4]] (bacteriophage T7, DNA replication).
*'''Rho-like family''': Rho (E. coli, transcription termination).
Note: These superfamilies do not subsume all possible helicases. For example [[XPB]] and [[ERCC2]] are helicases not included in any of the above families.
==References==
<references/>
*Anand SP, Zheng H, Bianco PR, Leuba SH, Khan SA. DNA helicase activity of PcrA is not required for displacement of RecA protein from DNA or inhibition of RecA-mediated DNA strand exchange. Journal of Bacteriology (2007) 189 (12):4502-4509.
* Bird L, Subramanya HS, Wigley DB, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9519291&query_hl=40&itool=pubmed_docsum|"Helicases: a unifying structural theme?"], Current Opinion in Structural Biology. 1998 Feb; 8 (1): 14-18.
* Betterton MD, Julicher F, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15697627&query_hl=43&itool=pubmed_docsum|"Opening of nucleic-acid double strands by helicases: active versus passive opening."], [[Physical Review|Physical Review E]]. 2005 Jan; 71 (1): 011904.
==External links==
* {{MeshName|DNA+Helicases}}
* {{MeshName|RNA+Helicases}}
{{Enzymes}}
{{DNA replication}}
[[Category:EC 3.6.1]]
[[Category:DNA replication]]
[[Category:Enzymes]]
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