Skip to main content

APOBEC deaminases-mutases with defensive roles for immunity

Science in China Series C: Life Sciences volume 52, pages 893–902 (2009)Cite this article

Abstract

In recent years, tremendous progress has been made in the elucidation of the biological roles and molecular mechanisms of the apolioprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of enzymes. The APOBEC family of cytidine deaminases has important functional roles within the adaptive and innate immune system. Activation induced cytidine deaminase (AID) plays a central role in the biochemical steps of somatic hypermutation and class switch recombination during antibody maturation, and the APOBEC 3 enzymes are able to inhibit the mobility of retroelements and the replication of retroviruses and DNA viruses, such as the human immunodeficiency virus type-1 and hepatitis B virus. Recent advances in structural and functional studies of the APOBEC enzymes provide new biochemical insights for how these enzymes carry out their biological roles. In this review, we provide an overview of these recent advances in the APOBEC field with a special emphasis on AID and APOBEC3G.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Jarmuz A, Chester A, Bayliss J, et al. An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics, 2002, 79: 285–296 11863358, 10.1006/geno.2002.6718, 1:CAS:528:DC%2BD38XhsVGhu7c%3D

    PubMed  CAS  Google Scholar 

  2. Franca R, Spadari S, Maga G. APOBEC deaminases as cellular antiviral factors: A novel natural host defense mechanism. Med Sci Monit, 2006, 12: RA92–RA98 16641889, 1:CAS:528:DC%2BD28XlsFamt74%3D

    PubMed  CAS  Google Scholar 

  3. OhAinle M, Kerns J A, Malik H S, et al. Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H. J Virol, 2006, 80: 3853–3862 16571802, 10.1128/JVI.80.8.3853-3862.2006, 1:CAS:528:DC%2BD28Xjs1Srtb8%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  4. Navarro F, Bollman B, Chen H, et al. Complementary function of the two catalytic domains of APOBEC3G. Virology, 2005, 333: 374–386 15721369, 10.1016/j.virol.2005.01.011, 1:CAS:528:DC%2BD2MXhsVOitLo%3D

    PubMed  CAS  Google Scholar 

  5. Newman E N, Holmes R K, Craig H M, et al. Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol, 2005, 15: 166–170 15668174, 10.1016/j.cub.2004.12.068, 1:CAS:528:DC%2BD2MXmvFeltA%3D%3D

    PubMed  CAS  Google Scholar 

  6. Iwatani Y, Takeuchi H, Strebel K, et al. Biochemical activities of highly purified, catalytically active human APOBEC3G: Correlation with antiviral effect. J Virol, 2006, 80: 5992–6002 16731938, 10.1128/JVI.02680-05, 1:CAS:528:DC%2BD28XlsFWmsbg%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  7. Liddament M T, Brown W L, Schumacher A J, et al. APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr Biol, 2004, 14: 1385–1391 15296757, 10.1016/j.cub.2004.06.050, 1:CAS:528:DC%2BD2cXmsVKmsrs%3D

    PubMed  CAS  Google Scholar 

  8. Bishop K N, Holmes R K, Sheehy A M, et al. Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Curr Biol, 2004,14: 1392–1396 15296758, 10.1016/j.cub.2004.06.057, 1:CAS:528:DC%2BD2cXmsVKmsrg%3D

    PubMed  CAS  Google Scholar 

  9. Bogerd H P, Wiegand H L, Doehle B P, et al. The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains. Virology, 2007, 364: 486–493 17434555, 10.1016/j.virol.2007.03.019, 1:CAS:528:DC%2BD2sXmtlSktbY%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  10. Okazaki I M, Hiai H, Kakazu N, et al. Constitutive expression of AID leads to tumorigenesis. J Exp Med, 2003, 197: 1173–1181 12732658, 10.1084/jem.20030275, 1:CAS:528:DC%2BD3sXjs1ygsLw%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  11. Kou T, Marusawa H, Kinoshita K, et al. Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis. Int J Cancer, 2007, 120: 469–476 17066440, 10.1002/ijc.22292, 1:CAS:528:DC%2BD28XhtlGqsrnF

    PubMed  CAS  Google Scholar 

  12. Komori J, Marusawa H, Machimoto T, et al. Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. Hepatology, 2008, 47: 888–896 18306229, 10.1002/hep.22125, 1:CAS:528:DC%2BD1cXktVOhsrs%3D

    PubMed  CAS  Google Scholar 

  13. Longerich S, Orelli B J, Martin R W, et al. Brca1 in immunoglobulin gene conversion and somatic hypermutation. DNA Repair (Amst), 2008, 7: 253–266 10.1016/j.dnarep.2007.10.002, 1:CAS:528:DC%2BD1cXisl2msw%3D%3D

    CAS  Google Scholar 

  14. Marusawa H. Aberrant AID expression and human cancer development. Int J Biochem Cell Biol, 2008, 40: 1399–1402 18329947, 10.1016/j.biocel.2008.01.018, 1:CAS:528:DC%2BD1cXlslGqtbY%3D

    PubMed  CAS  Google Scholar 

  15. Matsumoto Y, Marusawa H, Kinoshita K, et al. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med, 2007, 13: 470–476 17401375, 10.1038/nm1566, 1:CAS:528:DC%2BD2sXjvVaquro%3D

    PubMed  CAS  Google Scholar 

  16. Morisawa T, Marusawa H, Ueda Y, et al. Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. Int J Cancer, 2008, 123: 2735–2740 18781563, 10.1002/ijc.23853, 1:CAS:528:DC%2BD1cXhsVKgtrbK

    PubMed  CAS  Google Scholar 

  17. Chester A, Scott J, Anant S, et al. RNA editing: Cytidine to uridine conversion in apolipoprotein B mRNA. Biochim Biophys Acta, 2000, 1494: 1–13 11072063, 1:CAS:528:DC%2BD3MXptFaq

    PubMed  CAS  Google Scholar 

  18. Teng B, Burant C F, Davidson N O. Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science, 1993, 260: 1816–1819 8511591, 10.1126/science.8511591, 1:CAS:528:DyaK3sXltleksb4%3D

    PubMed  CAS  Google Scholar 

  19. Navaratnam N, Morrison J R, Bhattacharya S, et al. The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. J Biol Chem, 1993, 28: 20709–20712

    Google Scholar 

  20. Petersen-Mahrt S K, Neuberger M S. In vitro deamination of cytosine to uracil in single-stranded DNA by apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). J Biol Chem, 2003, 278: 19583–19586 12697753, 10.1074/jbc.C300114200, 1:CAS:528:DC%2BD3sXktVaqsLo%3D

    PubMed  CAS  Google Scholar 

  21. Anant S, Mukhopadhyay D, Sankaranand V, et al. ARCD-1, an apobec-1-related cytidine deaminase, exerts a dominant negative effect on C to U RNA editing. Am J Cell Physiol, 2001, 281: C1904–1916 1:CAS:528:DC%2BD3MXptlKms7s%3D

    CAS  Google Scholar 

  22. Rogozin I B, Basu M K, Jordan K I, et al. APOBEC4, a new member of the AID/APOBEC family of polynucleotide (Deoxy)cytidine deaminases predicted by computational analysis. Cell Cycle, 2005, 4: 1281–1285 16082223, 1:CAS:528:DC%2BD28XktVCgtbk%3D

    PubMed  CAS  Google Scholar 

  23. Peled J U, Kuang F L, Iglesias-Ussel M D, et al. The biochemistry of somatic hypermutation. Annu Rev Immunol, 2008, 26: 481–511 18304001, 10.1146/annurev.immunol.26.021607.090236, 1:CAS:528:DC%2BD1cXltlWktrw%3D

    PubMed  CAS  Google Scholar 

  24. Schrader C E, Guikema J E, Wu X, et al. The roles of APE1, APE2, DNA polymerase beta and mismatch repair in creating S region DNA breaks during antibody class switch. Philos Trans R Soc Lond B Biol Sci, 2009, 364: 645–652 19010771, 10.1098/rstb.2008.0200, 1:CAS:528:DC%2BD1MXjs1Wisbc%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Muramatsu M, Kinoshita K, Fagarasan S, et al. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell, 2000, 102: 553–563 11007474, 10.1016/S0092-8674(00)00078-7, 1:CAS:528:DC%2BD3cXmsFWit7g%3D

    PubMed  CAS  Google Scholar 

  26. Neuberger M S, Harris R S, Di Noia J M, et al. Immunity through DNA deamination. Trends Biochem Sci, 2003, 28: 305–312 12826402, 10.1016/S0968-0004(03)00111-7, 1:CAS:528:DC%2BD3sXkvVCnu7c%3D

    PubMed  CAS  Google Scholar 

  27. Bransteitter R, Pham P, Scharff M D, et al. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci USA, 2003, 100: 4102–4107 12651944, 10.1073/pnas.0730835100, 1:CAS:528:DC%2BD3sXivFSqu7k%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  28. Langlois M A, Beale R C L, Conticello S G, et al. Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases providing insight into their DNA target site specificities. Nucleic Acids Res, 2005, 33: 1913–1923 15809227, 10.1093/nar/gki343, 1:CAS:528:DC%2BD2MXjtlensbs%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  29. Pham P, Bransteitter R, Petruska J, et al. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature, 2003, 424: 103–107 12819663, 10.1038/nature01760, 1:CAS:528:DC%2BD3sXltVelsbs%3D

    PubMed  CAS  Google Scholar 

  30. Imai K, Slupphaug G, Lee W I, et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol, 2003, 4: 1023–1028 12958596, 10.1038/ni974, 1:CAS:528:DC%2BD3sXnsF2murc%3D

    PubMed  CAS  Google Scholar 

  31. Revy P, Muto T, Levy Y, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell, 2000, 102: 565–575 11007475, 10.1016/S0092-8674(00)00079-9, 1:CAS:528:DC%2BD3cXmsFWit7k%3D

    PubMed  CAS  Google Scholar 

  32. Durandy A, Peron S, Fischer A. Hyper-IgM syndromes. Curr Opin Rheumatol, 2006, 18: 369–376 16763457, 10.1097/01.bor.0000231905.12172.b5, 1:CAS:528:DC%2BD28XlsVeqsrc%3D

    PubMed  CAS  Google Scholar 

  33. Minegishi Y, Lavoie A, Cunningham-Rundles C, et al. Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome. Clin Immunol, 2000, 97: 203–210 11112359, 10.1006/clim.2000.4956, 1:CAS:528:DC%2BD3MXkvVKhsQ%3D%3D

    PubMed  CAS  Google Scholar 

  34. Sheehy A M, Gaddis N C, Choi J D, et al. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature, 2002, 418: 646–650 12167863, 10.1038/nature00939, 1:CAS:528:DC%2BD38XlvVyltLs%3D

    PubMed  CAS  Google Scholar 

  35. Alce T M, Popik W. APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem, 2004, 279: 34083–34086 15215254, 10.1074/jbc.C400235200, 1:CAS:528:DC%2BD2cXmvFensbk%3D

    PubMed  CAS  Google Scholar 

  36. Luo K, Lui B, Xiao Z, et al. Amino-terminal region of the human immunodeficiency virus type 1 nucleo-capsid is required for human APOBEC3G packaging. J Virol, 2004, 78: 11841–11852 15479826, 10.1128/JVI.78.21.11841-11852.2004, 1:CAS:528:DC%2BD2cXptVKls7Y%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  37. Zennou V D, Perez-Caballero D, Gottlinger H, et al. APOBEC3G incorporation into human immunodeficiency virus type 1 particles. J Virol, 2004, 78: 12058–12061 15479846, 10.1128/JVI.78.21.12058-12061.2004, 1:CAS:528:DC%2BD2cXptVKlsbY%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  38. Scharfer A, Bogerd H P, Cullen B R. Specific packaging of APOBEC3G into HIV-1 virions is mediated by the nucleocapsid domain of the gag polyprotein precursor. Virology, 2004, 328: 163–168 10.1016/j.virol.2004.08.006, 1:CAS:528:DC%2BD2cXotF2nur0%3D

    Google Scholar 

  39. Burnett A, Spearman P. APOBEC3G multimers are recruited to the plasma membrane for packaging into human immunodeficiency virus type 1 virus-like particles in an RNA-dependent process requiring the NC basic linker. J Virol, 2007, 81: 5000–5013 17344295, 10.1128/JVI.02237-06, 1:CAS:528:DC%2BD2sXls1Grs7s%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  40. Suspene R, Sommer P, Henry M, et al. APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res, 2004, 32: 2421–2429 15121899, 10.1093/nar/gkh554, 1:CAS:528:DC%2BD2cXktVahsrw%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  41. Yu Q, Konig R, Pillai S, et al. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol, 2004, 11: 435–442 15098018, 10.1038/nsmb758, 1:CAS:528:DC%2BD2cXjsVCqsL4%3D

    PubMed  CAS  Google Scholar 

  42. Guo F, Cen S, Niu M, et al. The interaction of APOBEC3G with human immunodeficiency virus type 1 nucleocapsid inhibits tRNA3Lys annealing to viral RNA. J Virol, 2007, 81: 11322–11331 17670826, 10.1128/JVI.00162-07, 1:CAS:528:DC%2BD2sXhtFeltL7F

    PubMed Central  PubMed  CAS  Google Scholar 

  43. Iwatani Y, Chan D S B, Wang F, et al. Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res, 2007, 35: 7096–7108 17942420, 10.1093/nar/gkm750, 1:CAS:528:DC%2BD1cXhtFGqsg%3D%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  44. Li X-Y, Guo F, Zhang L, et al. APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem, 2007, 282: 32065–32074 17855362, 10.1074/jbc.M703423200, 1:CAS:528:DC%2BD2sXht1Wls7%2FN

    PubMed  CAS  Google Scholar 

  45. Luo K, Wang T, Liu B, et al. Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol, 2007, 81: 7238–7248 17428847, 10.1128/JVI.02584-06, 1:CAS:528:DC%2BD2sXntVOit7o%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  46. Mbisa J L, Barr R, Thomas J A, et al. Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit effects in plus-strand DNA transfer and integration. J Virol, 2007, 81: 7099–7110 17428871, 10.1128/JVI.00272-07, 1:CAS:528:DC%2BD2sXntVOitr4%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Doehle B P, Schafer A, Cullen B R. Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. Virology, 2005, 339: 281–288 15993456, 10.1016/j.virol.2005.06.005, 1:CAS:528:DC%2BD2MXos1Wqs7Y%3D

    PubMed  CAS  Google Scholar 

  48. Gooch B D, Cullen B R. Functional domain organization of human APOBEC3G. Virology, 2008, 379: 118–124 18639915, 10.1016/j.virol.2008.06.013, 1:CAS:528:DC%2BD1cXhtVWitL3I

    PubMed Central  PubMed  CAS  Google Scholar 

  49. Bourara K, Liegler T J, Grant R M. Target cell APOBEC3C can induce limited G-to-A mutation in HIV-1. PLoS Pathog, 2007, 3: 1477–1485 17967058, 10.1371/journal.ppat.0030153, 1:CAS:528:DC%2BD2sXhsVOgu7jK

    PubMed  CAS  Google Scholar 

  50. Dang Y, Wang X, Esselman W J, et al. Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family. J Virol, 2006, 80: 10522–10533 16920826, 10.1128/JVI.01123-06, 1:CAS:528:DC%2BD28XhtFygsLfM

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Yu Q, Chen D, Konig R, et al. APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem, 2004, 279: 53379–53386 15466872, 10.1074/jbc.M408802200, 1:CAS:528:DC%2BD2cXhtVKqu77M

    PubMed  CAS  Google Scholar 

  52. Goila-Gaur R, Khan M A, Miyagi E, et al. Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity. Retrovirology, 2007, 4: 61 17727729, 10.1186/1742-4690-4-61, 1:CAS:528:DC%2BD2sXhtV2gu77N

    PubMed Central  PubMed  Google Scholar 

  53. Miyagi E, Opi S, Takeuchi H, et al. Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1. J Virol, 2007, 81: 13346–13353 17928335, 10.1128/JVI.01361-07, 1:CAS:528:DC%2BD2sXhsValsbrM

    PubMed Central  PubMed  CAS  Google Scholar 

  54. Schumacher A J, Hache G, Macduff D A, et al. The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD, and human immunodeficiency virus type 1 restriction. J Virol, 2008, 82: 2652–2660 18184715, 10.1128/JVI.02391-07, 1:CAS:528:DC%2BD1cXjtVart74%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  55. Chen H, Lilley C E, Yu Q, et al. APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Curr Biol, 2006, 16: 480–485 16527742, 10.1016/j.cub.2006.01.031, 1:CAS:528:DC%2BD28Xit1yltb4%3D

    PubMed  CAS  Google Scholar 

  56. Noguchi C, Ishino H, Tsuge M, et al. G to A hypermutation of hepatitis B virus. Hepatology, 2005, 41: 626–633 15726649, 10.1002/hep.20580, 1:CAS:528:DC%2BD2MXisFCrs7g%3D

    PubMed  CAS  Google Scholar 

  57. Rosler C, Kock J, Kann M, et al. APOBEC-mediated interference with hepadnavirus production. Hepatology, 2005, 42: 310–309 10.1002/hep.20801, 1:CAS:528:DC%2BD2MXpt1eks70%3D

    Google Scholar 

  58. Kock J, Blum H E. Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H. J Gen Virol, 2008, 89: 1184–1191 18420796, 10.1099/vir.0.83507-0, 1:CAS:528:DC%2BD1cXlslClt7k%3D

    PubMed  Google Scholar 

  59. Suspene R, Guetard D, Henry M, et al. Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo. Proc Natl Acad Sci USA, 2005, 102: 8321–8326 15919829, 10.1073/pnas.0408223102, 1:CAS:528:DC%2BD2MXlsV2mtb4%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  60. Turelli P, Mangeat B, Jost S, et al. Inhibition of hepatitis B virus replication by APOBEC3G. Science, 2004, 303: 1829 15031497, 10.1126/science.1092066

    PubMed  Google Scholar 

  61. Vartanian J, Guetard D, Henry M, et al. Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions. Science, 2008, 320: 230–233 18403710, 10.1126/science.1153201, 1:CAS:528:DC%2BD1cXktlGjtLg%3D

    PubMed  CAS  Google Scholar 

  62. Santiago M L, Montano M, Benitez R, et al. Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science, 2008, 321: 1343–1346 18772436, 10.1126/science.1161121, 1:CAS:528:DC%2BD1cXhtVGkurrE

    PubMed Central  PubMed  CAS  Google Scholar 

  63. Esnault C, Heidmann O, Delebecque F, et al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature, 2005, 433: 430–433 15674295, 10.1038/nature03238, 1:CAS:528:DC%2BD2MXnt1Wisw%3D%3D

    PubMed  CAS  Google Scholar 

  64. Bogerd H P, Wiegand H L, Doehle B P, et al. APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells. Nucleic Acids Res, 2006, 34: 89–95 16407327, 10.1093/nar/gkj416, 1:CAS:528:DC%2BD28Xmsl2nuw%3D%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Dutko J A, Schafer A, Kenny A E, et al. Inhibition of yeast LTR retrotransposon by human APOBEC3 cytidine deaminases. Curr Biol, 2005, 15: 661–666 15823539, 10.1016/j.cub.2005.02.051, 1:CAS:528:DC%2BD2MXjtV2itr8%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  66. Schumacher A J, Nissley D V, Harris R S. APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proc Natl Acad Sci USA, 2005, 102: 9854–9859 16000409, 10.1073/pnas.0501694102, 1:CAS:528:DC%2BD2MXmsFarurk%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  67. Muckenfuss H, Hamdorf M, Held U, et al. APOBEC3 proteins inhibit human LINE-1 retrotransposition. J Biol Chem, 2006, 281: 22161–22172 16735504, 10.1074/jbc.M601716200, 1:CAS:528:DC%2BD28XnsVOmtLk%3D

    PubMed  CAS  Google Scholar 

  68. Bogerd H P, Wiegand H L, Hulme A E, et al. Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc Natl Acad Sci USA, 2006, 103: 8780–8785 16728505, 10.1073/pnas.0603313103, 1:CAS:528:DC%2BD28XlvVCiu7k%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  69. Stenglein M D, Harris R S. APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism. J Biol Chem, 2006, 281: 16837–16841 16648136, 10.1074/jbc.M602367200, 1:CAS:528:DC%2BD28XlvVGlu7Y%3D

    PubMed  CAS  Google Scholar 

  70. Chiu Y L, Witkowska H E, Hall S C, et al. High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition. Proc Natl Acad Sci USA, 2006, 103: 15588–15593 17030807, 10.1073/pnas.0604524103, 1:CAS:528:DC%2BD28XhtFCjtLfP

    PubMed Central  PubMed  CAS  Google Scholar 

  71. Hulme A E, Bogerd H P, Cullen B R, et al. Selective inhibition of Alu retrotransposition by APOBEC3G. Gene, 2007, 390: 199–205 17079095, 10.1016/j.gene.2006.08.032, 1:CAS:528:DC%2BD2sXitV2qtr8%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  72. Chiu Y L, Greene W C. APOBEC3G: an intracellular centurion. Philos Trans R Soc Lond B Biol Sci, 2009, 364: 689–703 19008196, 10.1098/rstb.2008.0193, 1:CAS:528:DC%2BD1MXjs1Witr0%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  73. Prochnow C, Bransteitter R, Klein M G, et al. The APOBEC-2 crystal structure and functional implications for the deaminase AID. Nature, 2007, 445: 447–451 17187054, 10.1038/nature05492, 1:CAS:528:DC%2BD2sXos12mtA%3D%3D

    PubMed  CAS  Google Scholar 

  74. Brar S S, Sacho E J, Tessmer I, et al. Activation-induced deaminase, AID, is catalytically active as a monomer on single-stranded DNA. DNA Repair (Amst), 2008, 7: 77–87 10.1016/j.dnarep.2007.08.002, 1:CAS:528:DC%2BD2sXhsVSrsr7N

    PubMed Central  CAS  Google Scholar 

  75. Bhagwat A S, Carpenter M A, Bujnicki J M. Is AID a monomer in solution? DNA Repair (Amst), 2008, 7: 349–350 10.1016/j.dnarep.2007.10.009, 1:CAS:528:DC%2BD1cXitVOksbs%3D

    CAS  Google Scholar 

  76. Chelico L, Goodman M F. A model for oligomeric regulation of APOBEC3G cytosine deaminase-dependent restriction of HIV. J Biol Chem, 2008, 283: 13780–13791 18362149, 10.1074/jbc.M801004200, 1:CAS:528:DC%2BD1cXls12lsro%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  77. Wedekind J E, Gillilan R, Janda A, et al. Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular ribonucleoprotein particles from dimeric subunits. J Biol Chem, 2006, 281: 38122–38126 17079235, 10.1074/jbc.C600253200, 1:CAS:528:DC%2BD28Xht12nu7nI

    PubMed Central  PubMed  CAS  Google Scholar 

  78. Huthoff H, Autore F, Gallois-Montbrun S, et al. RNA-dependent oligomerization of APOBEC3G is required for restriction of HIV-1. PLoS Pathog, 2009, 5: e1000330 19266078, 10.1371/journal.ppat.1000330, 1:CAS:528:DC%2BD1MXjtFyjsLg%3D

    PubMed Central  PubMed  Google Scholar 

  79. Bennett R P, Salter J D, Liu X, et al. APOBEC3G subunits self-associate via the C-terminal deaminase domain. J Biol Chem, 2008, 283: 33329–33336 18842592, 10.1074/jbc.M803726200, 1:CAS:528:DC%2BD1cXhsVSgt7zO

    PubMed Central  PubMed  CAS  Google Scholar 

  80. Holden L G, Prochnow C, Chang P Y, et al. Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature, 2008, 456: 121–124 18849968, 10.1038/nature07357, 1:CAS:528:DC%2BD1cXhtlCjt77N

    PubMed Central  PubMed  CAS  Google Scholar 

  81. Chen K M, Harjes E, Gross P J, et al. Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature, 2008, 452: 116–119 18288108, 10.1038/nature06638, 1:CAS:528:DC%2BD1cXivFynurg%3D

    PubMed  CAS  Google Scholar 

  82. Bishop K N, Holmes R K, Sheehy A M, et al. APOBEC-mediated editing of viral RNA. Science, 2004, 305: 645 15286366, 10.1126/science.1100658, 1:CAS:528:DC%2BD2cXmt1Sgtrc%3D

    PubMed  CAS  Google Scholar 

  83. Petit V, Guetard D, Renard M, et al. Murine APOBEC1 is a powerful mutator of retroviral and cellular RNA in vitro and in vivo. J Mol Biol, 2009, 385: 65–78 18983852, 10.1016/j.jmb.2008.10.043, 1:CAS:528:DC%2BD1cXhsFCmsbnO

    PubMed  CAS  Google Scholar 

  84. Mehta A, Kinter M T, Sherman N E, et al. Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA. Mol Cell Biol, 2000, 20: 1846–1854 10669759, 10.1128/MCB.20.5.1846-1854.2000, 1:CAS:528:DC%2BD3cXhtF2ntLc%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  85. Chiu Y L, Soros V B, Kreisberg J F, et al. Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature, 2005, 435: 108–114 15829920, 10.1038/nature03493, 1:CAS:528:DC%2BD2MXjvVKntbY%3D

    PubMed  CAS  Google Scholar 

  86. Furukawa A, Nagata T, Matsugami A, et al. Structure, interaction and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G. EMBO J, 2009, 28: 440–451 19153609, 10.1038/emboj.2008.290, 1:CAS:528:DC%2BD1MXntFGguw%3D%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  87. Chelico L, Pham P, Calabrese P, et al. APOBEC3G DNA deaminase acts processively 3′ → 5′ on single-stranded DNA. Nat Struc Mol Biol, 2006, 13: 392–399 10.1038/nsmb1086, 1:CAS:528:DC%2BD28XltFWlsr0%3D

    CAS  Google Scholar 

  88. Harris R S, Bishop K N, Sheehy A M, et al. DNA deamination mediates innate immunity to retroviral infection. Cell, 2003, 113: 803–809 12809610, 10.1016/S0092-8674(03)00423-9, 1:CAS:528:DC%2BD3sXkvVektLo%3D

    PubMed  CAS  Google Scholar 

  89. Conticello S G, Langlois M A, Yang Z, et al. DNA deamination in immunity: AID in the context of its APOBEC relatives. Adv Immunol, 2007, 94: 37–73 17560271, 10.1016/S0065-2776(06)94002-4, 1:CAS:528:DC%2BD1cXisVKqsbo%3D

    PubMed  CAS  Google Scholar 

  90. Harris R S, Petersen-Mahrt S K, Neuberger M S. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell, 2002, 10: 1247–1253 12453430, 10.1016/S1097-2765(02)00742-6, 1:CAS:528:DC%2BD38Xptl2ktrs%3D

    PubMed  CAS  Google Scholar 

  91. Chen H, Lilley C E, Yu Q, et al. APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Curr Biol, 2006, 16: 480–485 16527742, 10.1016/j.cub.2006.01.031, 1:CAS:528:DC%2BD28Xit1yltb4%3D

    PubMed  CAS  Google Scholar 

  92. Kohli R M, Abrams S R, Gajula K S, et al. A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. J Biol Chem, 2009, 284: 22898–22904 19561087, 10.1074/jbc.M109.025536, 1:CAS:528:DC%2BD1MXpvFKitbo%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  93. Chelico L, Pham P, Goodman M F. Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA. Nat Struct Mol Biol, 2009, 16: 454–455 19421154, 10.1038/nsmb0509-454, 1:CAS:528:DC%2BD1MXlsVGgs7k%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  94. Nowarski R, Britan-Rosich E, Shiloach T, et al. Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase. Nat Struct Mol Biol, 2008, 15: 1059–1066 18820687, 10.1038/nsmb.1495, 1:CAS:528:DC%2BD1cXht1Sisb7O

    PubMed  CAS  Google Scholar 

  95. Pham P, Bransteitter R, Goodman M F. Reward versus risk: DNA cytidine deaminases triggering immunity and disease. Biochemistry, 2005, 44: 2703–2715 15723516, 10.1021/bi047481+, 1:CAS:528:DC%2BD2MXptlSjug%3D%3D

    PubMed  CAS  Google Scholar 

  96. Rada C, Di Noia J M, Neuberger M S. Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol Cell, 2004, 16: 163–171 15494304, 10.1016/j.molcel.2004.10.011, 1:CAS:528:DC%2BD2cXhtVWit7zM

    PubMed  CAS  Google Scholar 

  97. Zhu Y, Nonoyama S, Morio T, et al. Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase. J Med Dent Sci, 2003, 50: 41–46 12715918

    PubMed  Google Scholar 

  98. Basu U, Chaudhuri J, Alpert C, et al. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature, 2005, 438: 508–511 16251902, 10.1038/nature04255, 1:CAS:528:DC%2BD2MXht1Gis7nO

    PubMed  CAS  Google Scholar 

  99. Basu U, Chaudhuri J, Phan R T, et al. Regulation of activation induced deaminase via phosphorylation. Adv Exp Med Biol, 2007, 596: 129–137 17338181, 10.1007/0-387-46530-8_11

    PubMed  Google Scholar 

  100. Pasqualucci L, Kitaura Y, Gu H, et al. PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells. Proc Natl Acad Sci USA, 2006, 103: 395–400 16387847, 10.1073/pnas.0509969103, 1:CAS:528:DC%2BD28XpsVSlsw%3D%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  101. McBride K M, Gazumyan A, Woo E M, et al. Regulation of hypermutation by activation-induced cytidine deaminase phosphorylation. Proc Natl Acad Sci USA, 2006, 103: 8798–8803 16723391, 10.1073/pnas.0603272103, 1:CAS:528:DC%2BD28XlvVChsr4%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  102. Pham P, Smolka M B, Calabrese P, et al. Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase. J Biol Chem, 2008, 283: 17428–17439 18417471, 10.1074/jbc.M802121200, 1:CAS:528:DC%2BD1cXntFSnur0%3D

    PubMed Central  PubMed  CAS  Google Scholar 

  103. Arnold K, Bordoli L, Kopp J, et al. The SWISS-MODEL Workspace: A web-based environment for protein structure homolgy modelling. Bioinformatics, 2006, 22: 195–201 16301204, 10.1093/bioinformatics/bti770, 1:CAS:528:DC%2BD28XovVCltw%3D%3D

    PubMed  CAS  Google Scholar 

  104. DeLano W L. The PyMOL Molecular Graphics System: DeLano Scientific, 2002

Download references

Author information

Affiliations

  1. Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA

    Courtney Prochnow, Ronda Bransteitter & XiaoJiang S. Chen

Authors
  1. Courtney Prochnow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronda Bransteitter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. XiaoJiang S. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to XiaoJiang S. Chen.

Additional information

Supported by the National Institute of Health Grant (Grant No. R01GM087986)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Prochnow, C., Bransteitter, R. & Chen, X.S. APOBEC deaminases-mutases with defensive roles for immunity. SCI CHINA SER C 52, 893–902 (2009). https://doi.org/10.1007/s11427-009-0133-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-009-0133-1

Keywords

  • APOBEC
  • cytidine deaminase
  • activation induced cytidine deamination
  • somatic hypermutation
  • class switch recombination
  • HyperIgM 2 syndrome
  • human immunodeficiency virus (HIV)
  • DNA deamination