Helicases have been classified in 5 superfamilies (SF1-SF5) . 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 . 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>) . 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 .
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
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
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 .
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.
May 2006 / First entry.
PROSITE method (with tools and information) covered by this documentation:
Gorbalenya A.E. and Koonin E.V. .
Helicases: amino acid sequence comparisons and structure-function relationships.
Curr. Opin. Struct. Biol. 3:419-429(1993).
LeBowitz J.H. McMacken R.
The Escherichia coli dnaB replication protein is a DNA helicase.
Spelbrink 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.
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
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