Home  |  Contact
PROSITE documentation PDOC51199

Superfamily 4 helicase domain profile





Description

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 4 helicase, related to bacterial dnaB proteins, comprises a relatively small compact family of proteins containing, in addition to Walker A and B, three distinct conserved motifs which are not present in other helicase superfamilies. SF4 is a hexameric helicase that function mainly in bacterial or bacteriophage DNA replication. It is intimately associated with other proteins of the replication fork. The helicase domain assembles into ring-shaped hexamers that encircle the lagging strand of the replication fork, moving in a 5' to 3' direction and displacing the complementary DNA strand in an unwinding reaction that is powered by nucleotide hydrolysis [2,3].

Several bacteriophage SF4 helicase domains have been crystalized (see for example <PDB:1CR0>) [4]. The central core is similar to the α-β RecA-like domain. The functional enzyme is arranged in a ring-shaped hexamer. A nucleotide binds in the crevice formed between adjacent subunits, where an arginine that is analogous to the arginine finger motif of GTPase-activating proteins (see <PDOC50238>) could trans-activate the bound nucleotide for hydrolysis. This nucleotide-binding site at the interface of two helicase domains is also a feature of other DNA helicase such as PcrA, Rep or NS3 proteins, and it could be a general mechanism for DNA unwinding activity [4].

Some proteins known to contain an SF4 helicase domain are listed below [5,6]:

  • Bacterial dnaB protein. It unwinds the DNA duplex ahead of the replication fork and is also responsible for attracting the dnaG primase to the replication fork.
  • Bacteriophage T7 gp4 and bacteriophage T4 gp41 proteins. They are bifunctional primase-helicases that unwind duplex DNA at the replication fork while initiating the synthesis of Okazaki fragments on the lagging strand.
  • Metazoan Twinkle proteins. In human, Twinkle is a helicase involved in mitochondrial DNA replication. It has been implicated in autosomal dominant progressive external ophthalmoplegia (adPEO), a mitochondrial disorder characterized by mtDNA deletions [7].
  • Several Cryptophyta and Viridiplantae hypothetical proteins that also contain a primase domain.
  • Several protozoan hypothetical proteins that also contain a primase domain or an exonuclease domain.
  • Rhodophyta chloroplastic dnaB-like proteins.

The profile we developed covers the entire SF4 helicase domain.

Last update:

May 2006 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

SF4_HELICASE, PS51199; Superfamily 4 helicase domain profile  (MATRIX)


References

1AuthorsGorbalenya A.E. and Koonin E.V. .
TitleHelicases: amino acid sequence comparisons and structure-function relationships.
SourceCurr. Opin. Struct. Biol. 3:419-429(1993).

2AuthorsLeBowitz J.H. McMacken R.
TitleThe Escherichia coli dnaB replication protein is a DNA helicase.
SourceJ. Biol. Chem. 261:4738-4748(1986).
PubMed ID3007474

3AuthorsAhnert P. Patel S.S.
TitleAsymmetric interactions of hexameric bacteriophage T7 DNA helicase with the 5'- and 3'-tails of the forked DNA substrate.
SourceJ. Biol. Chem. 272:32267-32273(1997).
PubMed ID9405431

4AuthorsSawaya M.R. Guo S. Tabor S. Richardson C.C. Ellenberger T.
TitleCrystal structure of the helicase domain from the replicative helicase-primase of bacteriophage T7.
SourceCell 99:167-177(1999).
PubMed ID10535735

5AuthorsLeipe D.D. Aravind L. Grishin N.V. Koonin E.V.
TitleThe bacterial replicative helicase DnaB evolved from a RecA duplication.
SourceGenome Res. 10:5-16(2000).
PubMed ID10645945

6AuthorsShutt T.E. Gray M.W.
TitleTwinkle, the mitochondrial replicative DNA helicase, is widespread in the eukaryotic radiation and may also be the mitochondrial DNA primase in most eukaryotes.
SourceJ. Mol. Evol. 62:588-599(2006).
PubMed ID16612544
DOI10.1007/s00239-005-0162-8

7AuthorsSpelbrink J.N. Li F.Y. Tiranti V. Nikali K. Yuan Q.P. Tariq M. Wanrooij S. Garrido N. Comi G. Morandi L. Santoro L. Toscano A. Fabrizi G.M. Somer H. Croxen R. Beeson D. Poulton J. Suomalainen A. Jacobs H.T. Zeviani M. Larsson C.
TitleHuman mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
SourceNat. Genet. 28:223-231(2001).
PubMed ID11431692
DOI10.1038/90058



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)