Single-stranded binding protein

{{Infobox protein family

| Symbol = SSB

| Name = SSB

| image = PDB 1v1q EBI.jpg

| width =

| caption = Crystal structure of PriB- a primosomal DNA replication protein of Escherichia coli

| Pfam = PF00436

| Pfam_clan = CL0021

| InterPro = IPR000424

| SMART =

| PROSITE = PDOC00602

| MEROPS =

| SCOP = 1kaw

| TCDB = 3.A.7

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}{{Short description|Class of proteins}}

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

{{Infobox protein family

| Symbol = Viral_DNA_bp

| Name = Viral_DNA_bp

| image = PDB 1urj EBI.jpg

| width =

| caption = Single stranded DNA-binding protein(icp8) from herpes simplex virus-1

| Pfam = PF00747

| Pfam_clan =

| InterPro = IPR000635

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

Although the overall picture of human cytomegalovirus (HHV-5) DNA synthesis appears typical of the herpesviruses, some novel features are emerging.

=Structure=

In ICP8, the herpes simplex virus (HSV-1) single-strand DNA-binding protein (ssDNA-binding protein (SSB)), the head consists of the eight alpha helices. The front side of the neck region consists of a five-stranded beta-sheet and two alpha helices, whereas the back side is a three-stranded beta-sheet The shoulder part of the N-terminal domain contains an alpha-helical and beta-sheet region. The herpes simplex virus (HSV-1) SSB, ICP8, is a nuclear protein that, along other replication proteins is required for viral DNA replication during lytic infection.{{cite journal|vauthors=Mapelli M, Panjikar S, Tucker PA |title=The crystal structure of the herpes simplex virus 1 ssDNA-binding protein suggests the structural basis for flexible, cooperative single-stranded DNA binding |journal=J Biol Chem |year= 2005 |volume= 280 |issue= 4 |pages= 2990–7 |doi=10.1074/jbc.M406780200 |pmid=15507432|doi-access=free }}

=Mechanism=

Six herpes virus-group-common genes encode proteins that likely constitute the replication fork machinery, including a two-subunit DNA polymerase, a Helicase-primase complex and a single-stranded DNA-binding protein.{{cite journal |vauthors=Anders DG, McCue LA |title= The human cytomegalovirus genes and proteins required for DNA synthesis |journal= Intervirology |volume= 39 |issue= 5–6 |pages= 378–88 |year= 1996 |pmid= 9130047 |doi= 10.1159/000150508}} The human herpesvirus 1 (HHV-1) single-strand DNA-binding protein ICP8 is a 128kDa zinc metalloprotein. Photoaffinity labeling has shown that the region encompassing amino acid residues 368-902 contains the single-strand DNA-binding site of ICP8.{{cite journal |vauthors=White EJ, Boehmer PE |title= Photoaffinity labeling of the herpes simplex virus type-1 single-strand DNA-binding protein (ICP8) with oligodeoxyribonucleotides |journal= Biochem. Biophys. Res. Commun. |volume= 264 |issue= 2 |pages= 493–7 |date=October 1999 |pmid= 10529391 |doi= 10.1006/bbrc.1999.1566 |doi-access= free }} The HHHV-1 UL5, UL8, and UL52 genes encode an essential heterotrimeric DNA helicase-primase that is responsible for concomitant DNA unwinding and primer 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.{{cite journal |vauthors=Tanguy Le Gac N, Villani G, Boehmer PE |title= Herpes simplex virus type-1 single-strand DNA-binding protein (ICP8) enhances the ability of the viral DNA helicase-primase to unwind cisplatin-modified DNA |journal= J. Biol. Chem. |volume= 273 |issue= 22 |pages= 13801–7 |date=May 1998 |pmid= 9593724 |doi= 10.1074/jbc.273.22.13801 |doi-access= free }}

Bacterial SSB

SSB protein domains in bacteria are important maintaining DNA metabolism, more specifically DNA replication, repair and recombination.{{cite journal |vauthors=Meyer RR, Laine PS |title=The single-stranded DNA-binding protein of Escherichia coli |journal=Microbiol. Rev. |volume=54 |issue=4 |pages=342–80 |date=December 1990 |pmid=2087220 |pmc=372786 |doi= 10.1128/MMBR.54.4.342-380.1990}} It has a structure of three beta-strands to a single six-stranded beta-sheet to form a dimer.{{cite journal |vauthors=Raghunathan S, Ricard CS, Lohman TM, Waksman G |title=Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli single-stranded DNA-binding protein determined by multiwavelength x-ray diffraction on the selenomethionyl protein at 2.9-A resolution |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=13 |pages=6652–7 |date=June 1997 |pmid=9192620 |pmc=21213 |doi= 10.1073/pnas.94.13.6652|doi-access=free }}

Eukaryotic replication protein A

{{Infobox heteropolypeptide

| heteropolymer = Replication protein A

| polymer_type = heterotrimer

| protein_type =

| function = damaged DNA binding, single-stranded DNA binding

| cofactors =

| image = 1L1O Replication protein A.png

| image_source = This is an image of human Replication protein A. From {{PDB|1L1O}} {{Proteopedia|Replication protein A}}

| SubunitCount = 3

| subunit1 = Replication protein A1

| gene1 = RPA1

| locus1 = Chr. 17 [https://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=17p13.3 p13.3]

| subunit2 = Replication protein A2

| gene2 = RPA2

| locus2 = Chr. 1 [https://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=1p35.3 p35.3]

| subunit3 = Replication protein A3

| gene3 = RPA3

| locus3 = Chr. 7 [https://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=7p21.3 p21.3]

}}

Replication protein A 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.{{cite journal|last1=Tiranti|first1=V|last2=Rocchi|first2=M|last3=DiDonato|first3=S|last4=Zeviani|first4=M|title=Cloning of human and rat cDNAs encoding the mitochondrial single-stranded DNA-binding protein (SSB).|journal=Gene|date=30 April 1993|volume=126|issue=2|pages=219–25|pmid=8482537|doi=10.1016/0378-1119(93)90370-i}} Human mtSSB is encoded by the SSBP1 gene. In yeast, it is encoded by the RIM1 gene.{{cite journal|last1=Van Dyck|first1=E|last2=Foury|first2=F|last3=Stillman|first3=B|last4=Brill|first4=SJ|title=A single-stranded DNA binding protein required for mitochondrial DNA replication in S. cerevisiae is homologous to E. coli SSB.|journal=The EMBO Journal|date=September 1992|volume=11|issue=9|pages=3421–30|pmid=1324172|pmc=556877|doi=10.1002/j.1460-2075.1992.tb05421.x}}

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.{{cite journal |last1=Pfeifer |first1=Matthias |last2=Brem |first2=Reto |last3=Lippert |first3=Timothy P. |last4=Boulianne |first4=Bryant |last5=Ho |first5=Howin Ng |last6=Robinson |first6=Mark E. |last7=Stebbing |first7=Justin |last8=Feldhahn |first8=Niklas |title=SSB1/SSB2 Proteins Safeguard B Cell Development by Protecting the Genomes of B Cell Precursors |journal=The Journal of Immunology |date=15 June 2019 |volume=202 |issue=12 |pages=3423–3433 |doi=10.4049/jimmunol.1801618 |pmid=31085591 |pmc=6545462 }}{{cite journal |last1=Shi |first1=Wei |last2=Vu |first2=Therese |last3=Boucher |first3=Didier |last4=Biernacka |first4=Anna |last5=Nde |first5=Jules |last6=Pandita |first6=Raj K. |last7=Straube |first7=Jasmin |last8=Boyle |first8=Glen M. |last9=Al-Ejeh |first9=Fares |last10=Nag |first10=Purba |last11=Jeffery |first11=Jessie |last12=Harris |first12=Janelle L. |last13=Bain |first13=Amanda L. |last14=Grzelak |first14=Marta |last15=Skrzypczak |first15=Magdalena |last16=Mitra |first16=Abhishek |last17=Dojer |first17=Norbert |last18=Crosetto |first18=Nicola |last19=Cloonan |first19=Nicole |last20=Becherel |first20=Olivier J. |last21=Finnie |first21=John |last22=Skaar |first22=Jeffrey R. |last23=Walkley |first23=Carl R. |last24=Pandita |first24=Tej K. |last25=Rowicka |first25=Maga |last26=Ginalski |first26=Krzysztof |last27=Lane |first27=Steven W. |last28=Khanna |first28=Kum Kum |title=Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress |journal=Blood |date=4 May 2017 |volume=129 |issue=18 |pages=2479–2492 |doi=10.1182/blood-2016-06-725093 |pmid=28270450 |pmc=5418634 }}{{cite journal |last1=Pandita |first1=R. K. |last2=Chow |first2=T. T. |last3=Udayakumar |first3=D. |last4=Bain |first4=A. L. |last5=Cubeddu |first5=L. |last6=Hunt |first6=C. R. |last7=Shi |first7=W. |last8=Horikoshi |first8=N. |last9=Zhao |first9=Y. |last10=Wright |first10=W. E. |last11=Khanna |first11=K. K. |last12=Shay |first12=J. W. |last13=Pandita |first13=T. K. |title=Single-Strand DNA-Binding Protein SSB1 Facilitates TERT Recruitment to Telomeres and Maintains Telomere G-Overhangs |journal=Cancer Research |date=14 January 2015 |volume=75 |issue=5 |pages=858–869 |doi=10.1158/0008-5472.CAN-14-2289 |pmid=25589350 |pmc=4351820 }}