SAMHD1: Difference between revisions
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b. Histidine- Aspartic (HD) domain-containing protein 1: residues 164 – 319 aa.<ref name=" White2013">White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen L, Kim B, Brojatsch J, Diaz-Griffero F.“ Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1”. {{cite journal| title=Virology. 2013 Feb 5;436(1):81-90|pmid=23158101}}</ref><ref name=" Crow 2009">Crow YJ, Rehwinkel J. “Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity”. {{cite journal| title=Hum Mol Genet. 2009 Oct 15;18(R2):R130-6|pmid=19808788}}</ref> HD domains proteins are characterized by a doublet of histidine and aspartic acid catalyticresidues, and have been shown to possess putative nuclease, dGTP triphosphatase, phosphatase or phosphodiesterase activities. <ref name=" Ayinde 2012">Ayinde D, Casartelli N, Schwartz O. “Restricting HIV the SAMHD1 way: through nucleotide starvation”. {{cite journal| title=Nat Rev Microbiol. 2012 Oct;10(10):675-80|pmid=22926205}}</ref><ref name=" Aravind 1998">Aravind L, Koonin EV.“ The HD domain defines a new superfamily of metal-dependent phosphohydrolases”. {{cite journal| title=Trends Biochem Sci. 1998 Dec;23(12):469-72|pmid=9868367}}</ref> |
b. Histidine- Aspartic (HD) domain-containing protein 1: residues 164 – 319 aa.<ref name=" White2013">White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen L, Kim B, Brojatsch J, Diaz-Griffero F.“ Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1”. {{cite journal| title=Virology. 2013 Feb 5;436(1):81-90|pmid=23158101}}</ref><ref name=" Crow 2009">Crow YJ, Rehwinkel J. “Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity”. {{cite journal| title=Hum Mol Genet. 2009 Oct 15;18(R2):R130-6|pmid=19808788}}</ref> HD domains proteins are characterized by a doublet of histidine and aspartic acid catalyticresidues, and have been shown to possess putative nuclease, dGTP triphosphatase, phosphatase or phosphodiesterase activities. <ref name=" Ayinde 2012">Ayinde D, Casartelli N, Schwartz O. “Restricting HIV the SAMHD1 way: through nucleotide starvation”. {{cite journal| title=Nat Rev Microbiol. 2012 Oct;10(10):675-80|pmid=22926205}}</ref><ref name=" Aravind 1998">Aravind L, Koonin EV.“ The HD domain defines a new superfamily of metal-dependent phosphohydrolases”. {{cite journal| title=Trends Biochem Sci. 1998 Dec;23(12):469-72|pmid=9868367}}</ref> |
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A crystal structure of a SAMHD1 fragment comprising catalytic core reveals that the protein is dimeric. ( |
A crystal structure of a SAMHD1 fragment comprising catalytic core reveals that the protein is dimeric.<ref name=" Goldstone 2011">Goldstone DC, Ennis-Adeniran V, Hedden JJ, et. al “HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase”. {{cite journal| title= Nature. 2011 Nov 6;480(7377):379-82.|pmid= 22056990}}</ref> Also studies have shown that SAMHD1 oligomerizes and forms tetramers.<ref name=" Yan 2013">Yan J, Kaur S, Delucia M, Hao C, Mehrens J, Wang C, Golczak M, Palczewski K, Gronenborn AM, Ahn J, Skowronski J. “Tetramerization of SAMHD1 Is Required for Biological Activity and Inhibition of HIV Infection”. {{cite journal| title=J Biol Chem. 2013 Apr 12;288(15):10406-17|pmid= 23426366}}</ref> SAMHD1 is phosphorylated on residue T592 in cycling cells but that this phosphorylation is lost when cells are in a noncycling state. 13. <ref name=" White 2013">White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen LA, Kim B, Tuzova M, Diaz-Griffero F. “The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation”. {{cite journal| title=Cell Host Microbe. 2013 Apr 17;13(4):441-51|pmid= 23601106}}</ref> |
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==Function== |
==Function== |
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Revision as of 23:17, 17 May 2013
Template:PBB SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells,[1] macrophages[2] and monocytes.[3] It is an enzyme that exhibits phosphohydrolase activity,[4] converting nucleotide triphosphates to a nucleoside and triphosphate. In doing so, SAMHD1 depletes the pool of nucleotides available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication.[5]SAMHD1 also has nuclease activity
Nomenclature
SAMHD1 protein is also known as: • AGS5: Aicardi- Goutières syndrome type 5[6] • DCIP: Dendritic cell-derived IFNG-induced protein2[7] • Mg11: Interferon-gamma-inducible protein[7] • HDDC1: HD domain containing 1 • MOP-5: Monocyte protein 5 • SAMH1_HUMAN • SBBI88 • CHBL2
Gene
The gene encoding human SAMHD1 was originally identified in a human dendritic cell cDNA library as an orthologue of a mouse gene IFN-γ-induced gene Mg11.[7]The SAMHD1 gene is located on chromosome 20. SAMHD1 spans 59,532 bp of genomic sequence (chromosome 20:34,954,059–35,013,590) in 16 exons and encodes a 626 amino-acid (aa) protein with a molecular weight of 72.2 kDa.[8][9]SAMHD1 expressed in both cycling and noncycling cells, but the antiviral activity of SAMHD1 is limited to noncycling cells.[10]
Structure
The SAMHD1 is 626 amino acids (aa) long and has 2 domains:
a. Sterile Alpha Motif (SAM) domain: residues 45 – 110 aa.[11][12] In general, SAM domains are known to function as protein–protein and protein–nucleic acid interactions in organisms from yeast to humans, docking sites for kinases, signal transduction and regulation of transcription.[13][14]
b. Histidine- Aspartic (HD) domain-containing protein 1: residues 164 – 319 aa.[11][12] HD domains proteins are characterized by a doublet of histidine and aspartic acid catalyticresidues, and have been shown to possess putative nuclease, dGTP triphosphatase, phosphatase or phosphodiesterase activities. [13][15]
A crystal structure of a SAMHD1 fragment comprising catalytic core reveals that the protein is dimeric.[16] Also studies have shown that SAMHD1 oligomerizes and forms tetramers.[17] SAMHD1 is phosphorylated on residue T592 in cycling cells but that this phosphorylation is lost when cells are in a noncycling state. 13. [18]
Function
Mutations in SAMHD1 are found in Aicardi–Goutières syndrome (AGS), “a hereditary autoimmune encephalopathy that is characterized by aberrant production of type I interferon (IFN) and symptoms mimicking congenital viral infection”. (7) Monocytes isolated from individuals with AGS are highly susceptible to HIV-1. (14) SAMHD1 was identified as a host protein that is bound and blocked by lentiviral protein, Vpx. Vpx promotes macrophage and DC infection by targeting SAMHD1. (15) Other studies identified SAMHD1 as the HIV-1 restriction factor in myeloid cells. (8, 16) The human SAMHD1 protein has dNTP triphosphatase activity, specifically dGTP-stimulated dNTP triphosphohydrolase activity, and nuclease activity against single-stranded DNA and RNA which is associated with its HD domain. (17, 18) Other studies demonstrated that silencing SAMHD1 enhanced HIV-1 and SIV Δvpx infection of myeloid cells, also enhances HIV-1 infection of resting CD4+ T cells. (5, 19)
Role in disease
Aicardi-Goutieres syndrome – related with mutations in the SAMHD1 gene.- 16 mutations in the SAMHD1 gene have been identified in patients with Aicardi-Goutieres syndrome. Mutations result in a SAMHD1 less functional protein. However, it is not known how this protein dysfunction leads to immune system abnormalities, inflammatory damage to the brain and skin, and other characteristics of this syndrome .(7, 14)
SAMHD1 restricts viral infection.- SAMHD1 was identified as the cellular protein responsible of the reverse transcription block to HIV-1 infection observed in myeloid cells as well as in quiescent CD4+ T cells. (16) SAMHD1 inhibits HIV-1 infection in myeloid cells by limiting the intracellular pool of dNTPs .(15) The dNTP triphosphohydrolase activity of SAMHD1 has been proposed to reduce the intracellular dNTP level, restricting HIV-1 replication and preventing activation of the immune system, a nuclease activity against single-stranded (ss)DNAs and RNAs, as well as against RNA in DNA/RNA hybrids. (8, 15) Retroviral restriction ability of SAMHD1 requires phosphorylation, for this purpose SAMHD1 associates with the cyclin A2/CDK1 complex that mediates its phosphorylation at threonine 592. (13)
References
- ^ Laguette, N. (2011). "SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx". Nature. PMID 21613998.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Hrecka, K. (2011). "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein". Nature. PMID 21720370.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Berger, A. (2011). "SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection". PLoS Phatog. PMID 22174685.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22056990, please use {{cite journal}} with
|pmid=22056990instead. - ^ Lahoussa, H.; et al. (2012). "SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates". Nature Immunology. 13: 223–228. doi:10.1038/ni.2236. PMID 22327569.
{{cite journal}}: Cite has empty unknown parameter:|month=(help); Explicit use of et al. in:|author=(help) - ^ Chahwan C, Chahwan R. “Aicardi-Goutieres syndrome: from patients to genes and beyond”. "Clin Genet. 2012 May;81(5):413-20". PMID 22149989.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b c Li N, Zhang W, Cao X. “Identification of human homologue of mouse IFN-gamma induced protein from human dendritic cells”. ". Immunol Lett. 2000 Nov 1;74(3):221-4". PMID 11064105.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, et. al. “Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response”. "Nat Genet. 2009 Jul;41(7):829-32". PMID 19525956.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Welbourn S, Miyagi E, White TE, Diaz-Griffero F, Strebel K. “Identification and characterization of naturally occurring splice variants of SAMHD1”. "Retrovirology. 2012 Oct 23;9:86". PMID 23092512.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, et. al. “SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells”. "Nat Med. 2012 Nov;18(11):1682-7". PMID 22972397.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen L, Kim B, Brojatsch J, Diaz-Griffero F.“ Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1”. "Virology. 2013 Feb 5;436(1):81-90". PMID 23158101.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b Crow YJ, Rehwinkel J. “Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity”. "Hum Mol Genet. 2009 Oct 15;18(R2):R130-6". PMID 19808788.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b Ayinde D, Casartelli N, Schwartz O. “Restricting HIV the SAMHD1 way: through nucleotide starvation”. "Nat Rev Microbiol. 2012 Oct;10(10):675-80". PMID 22926205.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Kim CA, Bowie JU.“ SAM domains: uniform structure, diversity of function”. "Trends Biochem Sci. 2003 Dec;28(12):625-8". PMID 14659692.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Aravind L, Koonin EV.“ The HD domain defines a new superfamily of metal-dependent phosphohydrolases”. "Trends Biochem Sci. 1998 Dec;23(12):469-72". PMID 9868367.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Goldstone DC, Ennis-Adeniran V, Hedden JJ, et. al “HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase”. "Nature. 2011 Nov 6;480(7377):379-82". PMID 22056990.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Yan J, Kaur S, Delucia M, Hao C, Mehrens J, Wang C, Golczak M, Palczewski K, Gronenborn AM, Ahn J, Skowronski J. “Tetramerization of SAMHD1 Is Required for Biological Activity and Inhibition of HIV Infection”. "J Biol Chem. 2013 Apr 12;288(15):10406-17". PMID 23426366.
{{cite journal}}: Cite journal requires|journal=(help) - ^ White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen LA, Kim B, Tuzova M, Diaz-Griffero F. “The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation”. "Cell Host Microbe. 2013 Apr 17;13(4):441-51". PMID 23601106.
{{cite journal}}: Cite journal requires|journal=(help)
Further reading
- Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22177690, please use {{cite journal}} with
|pmid=22177690instead. - Olsen JV, Blagoev B, Gnad F; et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Wistow G, Bernstein SL, Wyatt MK; et al. (2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Mol. Vis. 8: 205–20. PMID 12107410.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Deloukas P, Matthews LH, Ashurst J; et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Simpson JC, Wellenreuther R, Poustka A; et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link)
External links
- GeneReviews/NCBI/NIH/UW entry on Aicardi-Goutières Syndrome
- OMIM entries on Aicardi-Goutieres syndrome
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