Single-stranded Binding Protein
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Single-stranded binding proteins (SSBs) are a class of proteins that have been identified in both viruses and organisms from bacteria to humans.


Viral SSB

Although the overall picture of ''
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
'' (HHV-5) DNA synthesis appears typical of the herpesviruses, some novel features are emerging.


Structure

In ICP8, the
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
(HSV-1)
single-strand DNA-binding protein Single-strand DNA-binding protein (SSB) is a protein found in ''Escherichia coli'' (''E. coli'') bacteria, that binds to single-stranded regions of deoxyribonucleic acid ( DNA). Single-stranded DNA is produced during all aspects of DNA metabolism: ...
(ssDNA-binding protein (SSB)), the head consists of the eight
alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...
. The front side of the neck region consists of a five-stranded
beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
and two alpha helices, whereas the back side is a three-stranded beta-sheet The shoulder part of the
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
domain contains an alpha-helical and beta-sheet region. The
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
(HSV-1) SSB, ICP8, is a nuclear protein that, along other replication proteins is required for viral DNA replication during lytic infection.


Mechanism

Six herpes virus-group-common
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s encode
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s that likely constitute the replication fork machinery, including a two-subunit DNA polymerase, a Helicase-primase complex and a single-stranded DNA-binding protein. The ''
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
herpesvirus ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...
1'' (HHV-1) single-strand DNA-binding protein ICP8 is a 128kDa
zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
metalloprotein Metalloprotein is a generic term for a protein that contains a metal ion Cofactor (biochemistry), cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-bi ...
.
Photoaffinity labeling Photoaffinity labeling is a chemoproteomics technique used to attach "labels" to the active site of a large molecule, especially a protein. The "label" attaches to the molecule loosely and reversibly, and has an inactive site which can be converted ...
has shown that the region encompassing
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
residues 368-902 contains the single-strand DNA-binding site of ICP8. The HHHV-1 UL5, UL8, and UL52
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s encode an essential
heterotrimeric In biochemistry, a protein trimer is a macromolecular Complex (chemistry), complex formed by three, usually covalent bond, non-covalently bound, macromolecules like proteins or nucleic acids. A homotrimer would be formed by three identical molecul ...
DNA helicase-primase that is responsible for concomitant DNA unwinding and
primer Primer may refer to: Arts, entertainment, and media Films * ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth * ''Primer'' (video), a documentary about the funk band Living Colour Literature * Primer (textbook), a t ...
synthesis at the viral DNA replication fork. ICP8 may stimulate DNA unwinding and enable bypass of cisplatin damaged DNA by recruiting the helicase-primase to the DNA.


Bacterial SSB

SSB protein domains in
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
are important maintaining DNA metabolism, more specifically
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
, repair and recombination. It has a structure of three beta-strands to a single six-stranded
beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
to form a
dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ...
.


Eukaryotic replication protein A

Replication protein A Replication protein A (RPA) is the major protein that binds to single-stranded DNA (ssDNA) in eukaryotic cells. In vitro, RPA shows a much higher affinity for ssDNA than RNA or double-stranded DNA. RPA is required in replication, recombinatio ...
is the functional equivalent of SSB in the nucleus of eukaryotic cells, though there is no sequence homology.


Eukaryotic mitochondrial SSB

The mitochondria of eukaryotic cells contain their own single stranded DNA binding protein. Human mitochondrial SSB (mtSSB) binds to single-stranded mitochondrial DNA as a tetramer and has sequence similarity to bacterial SSB. Human mtSSB is encoded by the
SSBP1 Single-stranded DNA-binding protein, mitochondrial is a protein that in humans is encoded by the ''SSBP1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." ...
gene. In yeast, it is encoded by the RIM1 gene.


Role in Genome Repair and Anti-aging

Recently, it has been found that it 1. Helps protect the genome, 2. Is vital for stem cells and 3. Is involved with maintaining telomere length.


See also

*
DNA-binding protein DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for DNA#Base pairing, single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove ...
*
Replication protein A Replication protein A (RPA) is the major protein that binds to single-stranded DNA (ssDNA) in eukaryotic cells. In vitro, RPA shows a much higher affinity for ssDNA than RNA or double-stranded DNA. RPA is required in replication, recombinatio ...
*
Comparison of nucleic acid simulation software This is a list of notable computer programs that are used for nucleic acids simulations. See also References Computational chemistry software Software comparisons Molecular dynamics software Molecular modelling software {{sc ...


References


External links

*
SSB in PFAM
{{DNA replication Protein families DNA replication Proteins DNA-binding substances