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Crystal Structure of the DNA Deaminase APOBEC3B Catalytic Domain.

Shi K, Carpenter MA, Kurahashi K, Harris RS, Aihara H
J Biol Chem 290 28120-28130 (2015)
Related entries: 5cqd, 5cqh, 5cqi

Cited: 63 times
EuropePMC logo PMID: 26416889

Abstract

Functional and deep sequencing studies have combined to demonstrate the involvement of APOBEC3B in cancer mutagenesis. APOBEC3B is a single-stranded DNA cytosine deaminase that functions normally as a nuclear-localized restriction factor of DNA-based pathogens. However, it is overexpressed in cancer cells and elicits an intrinsic preference for 5'-TC motifs in single-stranded DNA, which is the most frequently mutated dinucleotide in breast, head/neck, lung, bladder, cervical, and several other tumor types. In many cases, APOBEC3B mutagenesis accounts for the majority of both dispersed and clustered (kataegis) cytosine mutations. Here, we report the first structures of the APOBEC3B catalytic domain in multiple crystal forms. These structures reveal a tightly closed active site conformation and suggest that substrate accessibility is regulated by adjacent flexible loops. Residues important for catalysis are identified by mutation analyses, and the results provide insights into the mechanism of target site selection. We also report a nucleotide (dCMP)-bound crystal structure that informs a multistep model for binding single-stranded DNA. Overall, these high resolution crystal structures provide a framework for further mechanistic studies and the development of novel anti-cancer drugs to inhibit this enzyme, dampen tumor evolution, and minimize adverse outcomes such as drug resistance and metastasis.

Reviews - 5cqk mentioned but not cited (1)

  1. A Novel Regulator of Activation-Induced Cytidine Deaminase/APOBECs in Immunity and Cancer: Schrödinger's CATalytic Pocket. King JJ, Larijani M. Front Immunol 8 351 (2017)

Articles - 5cqk mentioned but not cited (4)

  1. Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Shi K, Carpenter MA, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy JV, Demir Ö, Amaro RE, Harki DA, Harris RS, Aihara H. Nat Struct Mol Biol 24 131-139 (2017)
  2. Crystal Structure of the DNA Deaminase APOBEC3B Catalytic Domain. Shi K, Carpenter MA, Kurahashi K, Harris RS, Aihara H. J Biol Chem 290 28120-28130 (2015)
  3. Conformational Switch Regulates the DNA Cytosine Deaminase Activity of Human APOBEC3B. Shi K, Demir Ö, Carpenter MA, Wagner J, Kurahashi K, Harris RS, Amaro RE, Aihara H. Sci Rep 7 17415 (2017)
  4. Exploring ABOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer. Papini C, Wang Z, Kudalkar SN, Schrank TP, Tang S, Sasaki T, Wu C, Tejada B, Ziegler SJ, Xiong Y, Issaeva N, Yarbrough WG, Anderson KS. iScience 25 105077 (2022)


Reviews citing this publication (11)

  1. The APOBEC Protein Family: United by Structure, Divergent in Function. Salter JD, Bennett RP, Smith HC. Trends Biochem Sci 41 578-594 (2016)
  2. APOBEC Enzymes as Targets for Virus and Cancer Therapy. Olson ME, Harris RS, Harki DA. Cell Chem Biol 25 36-49 (2018)
  3. Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases. Siriwardena SU, Chen K, Bhagwat AS. Chem Rev 116 12688-12710 (2016)
  4. Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands. Salter JD, Smith HC. Trends Biochem Sci 43 606-622 (2018)
  5. RNA binding to APOBEC deaminases; Not simply a substrate for C to U editing. Smith HC. RNA Biol 14 1153-1165 (2017)
  6. The Role of APOBECs in Viral Replication. Xu WK, Byun H, Dudley JP. Microorganisms 8 E1899 (2020)
  7. Structural Insights into APOBEC3-Mediated Lentiviral Restriction. Delviks-Frankenberry KA, Desimmie BA, Pathak VK. Viruses 12 E587 (2020)
  8. The current toolbox for APOBEC drug discovery. Grillo MJ, Jones KFM, Carpenter MA, Harris RS, Harki DA. Trends Pharmacol Sci 43 362-377 (2022)
  9. Interactions of APOBEC3s with DNA and RNA. Maiti A, Hou S, Schiffer CA, Matsuo H. Curr Opin Struct Biol 67 195-204 (2021)
  10. Insights into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions. Chen XS. Viruses 13 497 (2021)
  11. Genetic differences between smokers and never-smokers with lung cancer. Kuśnierczyk P. Front Immunol 14 1063716 (2023)

Articles citing this publication (47)

  1. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer. Law EK, Sieuwerts AM, LaPara K, Leonard B, Starrett GJ, Molan AM, Temiz NA, Vogel RI, Meijer-van Gelder ME, Sweep FC, Span PN, Foekens JA, Martens JW, Yee D, Harris RS. Sci Adv 2 e1601737 (2016)
  2. The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis. Starrett GJ, Luengas EM, McCann JL, Ebrahimi D, Temiz NA, Love RP, Feng Y, Adolph MB, Chelico L, Law EK, Carpenter MA, Harris RS. Nat Commun 7 12918 (2016)
  3. Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. Kouno T, Silvas TV, Hilbert BJ, Shandilya SMD, Bohn MF, Kelch BA, Royer WE, Somasundaran M, Kurt Yilmaz N, Matsuo H, Schiffer CA. Nat Commun 8 15024 (2017)
  4. Letter Epstein-Barr virus BORF2 inhibits cellular APOBEC3B to preserve viral genome integrity. Cheng AZ, Yockteng-Melgar J, Jarvis MC, Malik-Soni N, Borozan I, Carpenter MA, McCann JL, Ebrahimi D, Shaban NM, Marcon E, Greenblatt J, Brown WL, Frappier L, Harris RS. Nat Microbiol 4 78-88 (2019)
  5. Crystal structures of APOBEC3G N-domain alone and its complex with DNA. Xiao X, Li SX, Yang H, Chen XS. Nat Commun 7 12193 (2016)
  6. The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism. Shaban NM, Shi K, Lauer KV, Carpenter MA, Richards CM, Salamango D, Wang J, Lopresti MW, Banerjee S, Levin-Klein R, Brown WL, Aihara H, Harris RS. Mol Cell 69 75-86.e9 (2018)
  7. Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA. Maiti A, Myint W, Kanai T, Delviks-Frankenberry K, Sierra Rodriguez C, Pathak VK, Schiffer CA, Matsuo H. Nat Commun 9 2460 (2018)
  8. Nuclear Magnetic Resonance Structure of the APOBEC3B Catalytic Domain: Structural Basis for Substrate Binding and DNA Deaminase Activity. Byeon IJ, Byeon CH, Wu T, Mitra M, Singer D, Levin JG, Gronenborn AM. Biochemistry 55 2944-2959 (2016)
  9. Family-Wide Comparative Analysis of Cytidine and Methylcytidine Deamination by Eleven Human APOBEC Proteins. Ito F, Fu Y, Kao SA, Yang H, Chen XS. J Mol Biol 429 1787-1799 (2017)
  10. A fluorescent reporter for quantification and enrichment of DNA editing by APOBEC-Cas9 or cleavage by Cas9 in living cells. St Martin A, Salamango D, Serebrenik A, Shaban N, Brown WL, Donati F, Munagala U, Conticello SG, Harris RS. Nucleic Acids Res 46 e84 (2018)
  11. BE-FLARE: a fluorescent reporter of base editing activity reveals editing characteristics of APOBEC3A and APOBEC3B. Coelho MA, Li S, Pane LS, Firth M, Ciotta G, Wrigley JD, Cuomo ME, Maresca M, Taylor BJM. BMC Biol 16 150 (2018)
  12. Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity. Hayward JA, Tachedjian M, Cui J, Cheng AZ, Johnson A, Baker ML, Harris RS, Wang LF, Tachedjian G. Mol Biol Evol 35 1626-1637 (2018)
  13. Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification. Pham P, Afif SA, Shimoda M, Maeda K, Sakaguchi N, Pedersen LC, Goodman MF. DNA Repair (Amst) 43 48-56 (2016)
  14. Enzyme cycling contributes to efficient induction of genome mutagenesis by the cytidine deaminase APOBEC3B. Adolph MB, Love RP, Feng Y, Chelico L. Nucleic Acids Res 45 11925-11940 (2017)
  15. Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H. Ito F, Yang H, Xiao X, Li SX, Wolfe A, Zirkle B, Arutiunian V, Chen XS. Sci Rep 8 3763 (2018)
  16. 1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure. Shaban NM, Shi K, Li M, Aihara H, Harris RS. J Mol Biol 428 2307-2316 (2016)
  17. Inhibiting APOBEC3 Activity with Single-Stranded DNA Containing 2'-Deoxyzebularine Analogues. Kvach MV, Barzak FM, Harjes S, Schares HAM, Jameson GB, Ayoub AM, Moorthy R, Aihara H, Harris RS, Filichev VV, Harki DA, Harjes E. Biochemistry 58 391-400 (2019)
  18. A Rabbit Monoclonal Antibody against the Antiviral and Cancer Genomic DNA Mutating Enzyme APOBEC3B. Brown WL, Law EK, Argyris PP, Carpenter MA, Levin-Klein R, Ranum AN, Molan AM, Forster CL, Anderson BD, Lackey L, Harris RS. Antibodies (Basel) 8 E47 (2019)
  19. Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation. Xiao X, Yang H, Arutiunian V, Fang Y, Besse G, Morimoto C, Zirkle B, Chen XS. Nucleic Acids Res 45 7494-7506 (2017)
  20. Biochemical Characterization of APOBEC3H Variants: Implications for Their HIV-1 Restriction Activity and mC Modification. Gu J, Chen Q, Xiao X, Ito F, Wolfe A, Chen XS. J Mol Biol 428 4626-4638 (2016)
  21. Computational Model and Dynamics of Monomeric Full-Length APOBEC3G. Gorle S, Pan Y, Sun Z, Shlyakhtenko LS, Harris RS, Lyubchenko YL, Vuković L. ACS Cent Sci 3 1180-1188 (2017)
  22. Molecular Interactions of a DNA Modifying Enzyme APOBEC3F Catalytic Domain with a Single-Stranded DNA. Fang Y, Xiao X, Li SX, Wolfe A, Chen XS. J Mol Biol 430 87-101 (2018)
  23. Protein kinase A inhibits tumor mutator APOBEC3B through phosphorylation. Matsumoto T, Shirakawa K, Yokoyama M, Fukuda H, Sarca AD, Koyabu S, Yamazaki H, Kazuma Y, Matsui H, Maruyama W, Nagata K, Tanabe F, Kobayashi M, Shindo K, Morishita R, Sato H, Takaori-Kondo A. Sci Rep 9 8307 (2019)
  24. Structural Analysis of the Active Site and DNA Binding of Human Cytidine Deaminase APOBEC3B. Hou S, Silvas TV, Leidner F, Nalivaika EA, Matsuo H, Kurt Yilmaz N, Schiffer CA. J Chem Theory Comput 15 637-647 (2019)
  25. NMR-based method of small changes reveals how DNA mutator APOBEC3A interacts with its single-stranded DNA substrate. Harjes S, Jameson GB, Filichev VV, Edwards PJB, Harjes E. Nucleic Acids Res 45 5602-5613 (2017)
  26. Structure-Based Design of First-Generation Small Molecule Inhibitors Targeting the Catalytic Pockets of AID, APOBEC3A, and APOBEC3B. King JJ, Borzooee F, Im J, Asgharpour M, Ghorbani A, Diamond CP, Fifield H, Berghuis L, Larijani M. ACS Pharmacol Transl Sci 4 1390-1407 (2021)
  27. Cryo-EM structure of the EBV ribonucleotide reductase BORF2 and mechanism of APOBEC3B inhibition. Shaban NM, Yan R, Shi K, Moraes SN, Cheng AZ, Carpenter MA, McLellan JS, Yu Z, Harris RS. Sci Adv 8 eabm2827 (2022)
  28. Simian Immunodeficiency Virus Vif and Human APOBEC3B Interactions Resemble Those between HIV-1 Vif and Human APOBEC3G. Wang J, Shaban NM, Land AM, Brown WL, Harris RS. J Virol 92 e00447-18 (2018)
  29. Determinants of Oligonucleotide Selectivity of APOBEC3B. Wagner JR, Demir Ö, Carpenter MA, Aihara H, Harki DA, Harris RS, Amaro RE. J Chem Inf Model 59 2264-2273 (2019)
  30. Letter Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates. Liu M, Mallinger A, Tortorici M, Newbatt Y, Richards M, Mirza A, van Montfort RLM, Burke R, Blagg J, Kaserer T. ACS Chem Biol 13 2427-2432 (2018)
  31. Flexibility in Nucleic Acid Binding Is Central to APOBEC3H Antiviral Activity. Bohn JA, DaSilva J, Kharytonchyk S, Mercedes M, Vosters J, Telesnitsky A, Hatziioannou T, Smith JL. J Virol 93 e01275-19 (2019)
  32. Structural basis of substrate specificity in human cytidine deaminase family APOBEC3s. Hou S, Lee JM, Myint W, Matsuo H, Kurt Yilmaz N, Schiffer CA. J Biol Chem 297 100909 (2021)
  33. Influence of the DNA sequence/length and pH on deaminase activity, as well as the roles of the amino acid residues around the catalytic center of APOBEC3F. Wan L, Nagata T, Katahira M. Phys Chem Chem Phys 20 3109-3117 (2018)
  34. Small-Angle X-ray Scattering Models of APOBEC3B Catalytic Domain in a Complex with a Single-Stranded DNA Inhibitor. Barzak FM, Ryan TM, Kvach MV, Kurup HM, Aihara H, Harris RS, Filichev VV, Harjes E, Jameson GB. Viruses 13 290 (2021)
  35. Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q. Shi K, Moeller NH, Banerjee S, McCann JL, Carpenter MA, Yin L, Moorthy R, Orellana K, Harki DA, Harris RS, Aihara H. Proc Natl Acad Sci U S A 118 e2021120118 (2021)
  36. Mechanism for APOBEC3G catalytic exclusion of RNA and non-substrate DNA. Solomon WC, Myint W, Hou S, Kanai T, Tripathi R, Kurt Yilmaz N, Schiffer CA, Matsuo H. Nucleic Acids Res 47 7676-7689 (2019)
  37. Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B. Shi K, Demir Ö, Carpenter MA, Banerjee S, Harki DA, Amaro RE, Harris RS, Aihara H. FASEB Bioadv 2 49-58 (2020)
  38. Targeting natural splicing plasticity of APOBEC3B restricts its expression and mutagenic activity. Rouf Banday A, Onabajo OO, Lin SH, Obajemu A, Vargas JM, Delviks-Frankenberry KA, Lamy P, Bayanjargal A, Zettelmeyer C, Florez-Vargas O, Pathak VK, Dyrskjøt L, Prokunina-Olsson L. Commun Biol 4 386 (2021)
  39. APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral infection. Manjunath L, Oh S, Ortega P, Bouin A, Bournique E, Sanchez A, Martensen PM, Auerbach AA, Becker JT, Seldin M, Harris RS, Semler BL, Buisson R. Nat Commun 14 820 (2023)
  40. APOBEC3B lysine residues are dispensable for DNA cytosine deamination, HIV-1 restriction, and nuclear localization. Molan AM, Hanson HM, Chweya CM, Anderson BD, Starrett GJ, Richards CM, Harris RS. Virology 511 74-81 (2017)
  41. Understanding the structural details of APOBEC3-DNA interactions using graph-based representations. Ng JC, Fraternali F. Curr Res Struct Biol 2 130-143 (2020)
  42. Identification of natural product 3, 5-diiodotyrosine as APOBEC3B inhibitor to prevent somatic mutation accumulation and cancer progression. Chen C, Sui X, Ning H, Sun Y, Du J, Chen X, Zhou X, Chen G, Shen W, Pang L, Zhou X, Shi R, Li W, Wang H, Zhao W, Zhai W, Qi Y, Wu Y, Gao Y. J Immunother Cancer 10 e005503 (2022)
  43. Structural Characterization of a Minimal Antibody against Human APOBEC3B. Tang H, Demir Ö, Kurniawan F, Brown WL, Shi K, Moeller NH, Carpenter MA, Belica C, Orellana K, Du G, LeBeau AM, Amaro RE, Harris RS, Aihara H. Viruses 13 663 (2021)
  44. APOBEC Reporter Systems for Evaluating diNucleotide Editing Levels. Rieffer AE, Chen Y, Salamango DJ, Moraes SN, Harris RS. CRISPR J 6 430-446 (2023)
  45. Computational Investigation of APOBEC3H Substrate Orientation and Selectivity. Hix MA, Cisneros GA. J Phys Chem B 124 3903-3908 (2020)
  46. Mechanisms for targeted, purposeful mutation revealed in an APOBEC-DNA complex. Schutsky EK, Hostetler ZM, Kohli RM. Nat Struct Mol Biol 24 97-98 (2017)
  47. Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer. Carpenter MA, Temiz NA, Ibrahim MA, Jarvis MC, Brown MR, Argyris PP, Brown WL, Starrett GJ, Yee D, Harris RS. PLoS Genet 19 e1011043 (2023)


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