Dispersed Sites of HIV Vif-Dependent Polyubiquitination in the DNA Deaminase APOBEC3F
Open accessAbstract
APOBEC3F (A3F) and APOBEC3G (A3G) are DNA cytosine deaminases that potently restrict human immunodeficiency virus type 1 replication when the virus is deprived of its accessory protein Vif (virion infectivity factor). Vif counteracts these restriction factors by recruiting A3F and A3G to an E3 ubiquitin (Ub) ligase complex that mediates their polyubiquitination (polyUb) and proteasomal degradation. While previous efforts have identified single amino acid residues in APOBEC3 proteins required for Vif recognition, less is known about the downstream Ub acceptor sites that are targeted. One prior report identified a cluster of polyubiquitinated residues in A3G and proposed an antiparallel model of A3G interaction with the Vif-E3 Ub ligase complex wherein Vif binding at one terminus of A3G orients the opposite terminus for polyUb [Iwatani et al. (2009). Proc. Natl. Acad. Sci. USA, 106, 19539-19544]. To test the generalizability of this model, we carried out a complete mutagenesis of the lysine residues in A3F and used a complementary, unbiased proteomic approach to identify Ub acceptor sites targeted by Vif. Our data indicate that internal lysines are the dominant Ub acceptor sites in both A3F and A3G. In contrast with the proposed antiparallel model, however, we find that the Vif-dependent polyUb of A3F and A3G can occur at multiple acceptor sites dispersed along predicted lysine-enriched surfaces of both the N- and C-terminal deaminase domains. These data suggest an alternative model for binding of APOBEC3 proteins to the Vif-E3 Ub ligase complex and diminish enthusiasm for the amenability of APOBEC3 Ub acceptor sites to therapeutic intervention.
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The Vif protein of HIV hijacks CRL5 and binds CBF-b, leading to degradation of A3F and A3G.
“For instance, the Vif protein of the human immunodeficiency virus (HIV) hijacks CRL5 and binds the cotranscription factor CBF-b leading to degradation of A3F and A3G, proteins that block viral replication.[95][96][97]”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [95]
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Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574 · see citing works
RING Domain E3 Ubiquitin Ligases
Deshaies, R. J., & Joazeiro, C. A. P. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.101807.093809 · Cited by 2,679 · see citing works
In Vivo Half-Life of a Protein Is a Function of Its Amino-Terminal Residue
Bachmair, A., Finley, D. J., & Varshavsky, A. J. (1986) · Science · doi:10.1126/science.3018930 · Cited by 1,976 · see citing works
Increasing the precision of comparative models with YASARA NOVA—a self‐parameterizing force field
Krieger, E., Koraimann, G., & Vriend, G. (2002) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10104 · Cited by 1,519 · see citing works
Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Zheng, N., Schulman, B. A., Song, L., Miller, J. J., Jeffrey, P. D., Wang, P., Chu, C., Koepp, D. M., Elledge, S. J., Pagano, M., et al. (2002) · Nature · doi:10.1038/416703a · Cited by 1,507 · see citing works
The N‐end rule pathway and regulation by proteolysis
Varshavsky, A. J. (2011) · Protein Science · doi:10.1002/pro.666 · Cited by 696 · see citing works
N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals
Hwang, C.-S., Shemorry, A., & Varshavsky, A. (2010) · Science · doi:10.1126/science.1183147 · Cited by 650 · see citing works
Structure of a β-TrCP1-Skp1-β-Catenin Complex
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00234-x · Cited by 612 · see citing works
Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination.
Scherer, D. C., Brockman, J. A., Chen, Z., Maniatis, T., & Ballard, D. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11259 · Cited by 554 · see citing works
Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling
Xu, G., Paige, J. S., & Jaffrey, S. R. (2010) · Nature Biotechnology · doi:10.1038/nbt.1654 · Cited by 534 · see citing works
Universality and Structure of the N-end Rule
Gonda, D. K., Bachmair, A., Wünning, I., Tobias, J. W., Lane, W. S., & Varshavsky, A. J. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84762-2 · Cited by 472 · see citing works
Chiu, Y., & Greene, W. C. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090350 · Cited by 417 · see citing works
Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection
Jäger, S., Kim, D. Y., Hultquist, J. F., Shindo, K., LaRue, R. S., Kwon, E., Li, M., Anderson, B. D., Yen, L., Stanley, D., et al. (2012) · Nature · doi:10.1038/nature10693 · Cited by 352 · see citing works
Self-citationWu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecules and Cells · Cited by 333 · see citing works
Schröfelbauer, B., Chen, D., & Landau, N. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307132101 · Cited by 309 · see citing works
Bogerd, H. P., Doehle, B., Wiegand, H. L., & Cullen, B. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307713101 · Cited by 295 · see citing works
APOBEC proteins and intrinsic resistance to HIV-1 infection
Malim, M. H. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0185 · Cited by 276 · see citing works
T-cell differentiation factor CBF-β regulates HIV-1 Vif-mediated evasion of host restriction
Zhang, W., Du, J., Evans, S. L., Yu, Y., & Yu, X.-F. (2011) · Nature · doi:10.1038/nature10718 · Cited by 265 · see citing works
A new reporter cell line to monitor HIV infection and drug susceptibility in vitro
Gervaix, A., West, D., Leoni, L. M., Richman, D. D., Wong‐Staal, F., & Corbeil, J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4653 · Cited by 256 · see citing works
Simon, V. R., Zennou, V., Murray, D., Huang, Y., Ho, D. D., & Bieniasz, P. D. (2005) · PLoS Pathogens · doi:10.1371/journal.ppat.0010006 · Cited by 249 · see citing works
氏家, 和., 石丸, 健., Barr, R., Zhang, Y., Khan, M. A., Strebel, K., & Pathak, V. K. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400830101 · Cited by 238 · see citing works
A Single Amino Acid Determinant Governs the Species-specific Sensitivity of APOBEC3G to Vif Action
Mangeat, B., Turelli, P., Liao, S., & Trono, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400060200 · Cited by 237 · see citing works
Russell, R. A., & Pathak, V. K. (2007) · Journal of Virology · doi:10.1128/jvi.00395-07 · Cited by 216 · see citing works
Towards a Functional Understanding of Protein N-Terminal Acetylation
Arnesen, T. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001074 · Cited by 197 · see citing works
Huthoff, H., & Malim, M. H. (2007) · Journal of Virology · doi:10.1128/jvi.02795-06 · Cited by 187 · see citing works
Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics
Albin, J. S., & Harris, R. S. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001343 · Cited by 185 · see citing works
Self-citationThe APOBEC3C crystal structure and the interface for HIV-1 Vif binding
Kitamura, S., Ode, H., Nakashima, M., et al. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2378 · Cited by 150 · see citing works
Crystal Structure of the APOBEC3G Catalytic Domain Reveals Potential Oligomerization Interfaces
Shandilya, S. M. D., Nalam, M. N. L., Nalivaika, E. A., Gross, P. J., Valesano, J. C., Shindo, K., Li, M., Munson, M., Royer, W. E., Harjes, E., et al. (2010) · Structure · doi:10.1016/j.str.2009.10.016 · Cited by 119 · see citing works
Self-citationAn Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model
Harjes, E., Gross, P. J., Chen, K., Lu, Y., Shindo, K., Nowarski, R., Gross, J. D., Kotler, M., Harris, R. S., & Matsuo, H. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.04.031 · Cited by 101 · see citing works
Self-citationRussell, R. A., Smith, J. L., Barr, R., Bhattacharyya, D., & Pathak, V. K. (2008) · Journal of Virology · doi:10.1128/jvi.01621-08 · Cited by 100 · see citing works
A Single Amino Acid Difference in Human APOBEC3H Variants Determines HIV-1 Vif Sensitivity
Zhen, A., Wang, T., Zhao, K., Xiong, Y., & Yu, X.-F. (2009) · Journal of Virology · doi:10.1128/jvi.01509-09 · Cited by 74 · see citing works
Iwatani, Y., Chan, D., Liu, L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906652106 · Cited by 70 · see citing works
Smith, J. L., & Pathak, V. K. (2010) · Journal of Virology · doi:10.1128/jvi.01437-10 · Cited by 70 · see citing works
Defects in DNA ligase I trigger PCNA ubiquitylation at Lys 107
Das‐Bradoo, S., Nguyen, H. D., Wood, J. L., Ricke, R. M., Haworth, J. C., & Bielinsky, A. (2009) · Nature Cell Biology · doi:10.1038/ncb2007 · Cited by 69 · see citing works
Zhang, W., Chen, G., Niewiadomska, A. M., Xu, R., & Yu, X.-F. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003963 · Cited by 62 · see citing works
Dang, Y., Siew, L. M., & Zheng, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708728200 · Cited by 60 · see citing works
Liu, J., & Nussinov, R. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000527 · Cited by 55 · see citing works
Flexible Cullins in Cullin-RING E3 Ligases Allosterically Regulate Ubiquitination
Liu, J., & Nussinov, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277236 · Cited by 52 · see citing works
Smith, J. L., Bu, W., Burdick, R. C., & Pathak, V. K. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.09.006 · Cited by 50 · see citing works
A Single Amino Acid in Human APOBEC3F Alters Susceptibility to HIV-1 Vif
Albin, J. S., LaRue, R. S., Weaver, J. A., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.173161 · Cited by 50 · see citing works
Self-citationDefinition of the interacting interfaces of Apobec3G and HIV-1 Vif using MAPPIT mutagenesis analysis
Lavens, D., Peelman, F., der Heyden, J. V., Uyttendaele, I., Catteeuw, D., Verhee, A., Schoubroeck, B. V., Kurth, J., Hallenberger, S., Clayton, R., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1154 · Cited by 49 · see citing works
Albin, J. S., Haché, G., Hultquist, J. F., et al. (2010) · Journal of Virology · doi:10.1128/jvi.00632-10 · Cited by 48 · see citing works
Self-citationLiu, J., & Nussinov, R. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.01.022 · Cited by 37 · see citing works
Wang, Y., Shao, Q., Yu, X., Kong, W., Hildreth, J. E. K., & Liu, B. (2011) · Journal of Virology · doi:10.1128/jvi.01925-10 · Cited by 27 · see citing works
Critical Role for Lysine 133 in the Nuclear Ubiquitin-mediated Degradation of MyoD
Batonnet‐Pichon, S., Leibovitch, M.-P., Tintignac, L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310315200 · Cited by 26 · see citing works
Bonifer, C., & Bowen, D. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001377 · Cited by 26 · see citing works
Polyubiquitination of APOBEC3G Is Essential for Its Degradation by HIV-1 Vif
Shao, Q., Wang, Y., Hildreth, J. E. K., et al. (2010) · Journal of Virology · doi:10.1128/jvi.01911-09 · Cited by 22 · see citing works
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Chasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200 · see citing works
Cullin E3 Ligases and Their Rewiring by Viral Factors
Mahon, C., Krogan, N., Craik, C., & Pick, E. (2014) · Biomolecules · doi:10.3390/biom4040897 · Cited by 101 · see citing works
Self-citation
- Authors
- Albin, J. S., Anderson, J. S., Johnson, J. R., Harjes, E., Matsuo, H., Krogan, N. J., & Harris, R. S.
- Affiliations
- University of Minnesota (US)
- Gladstone Institutes (US)
- Corresponding author
- Harris, Reuben S.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 425
- Issue
- 7
- Pages
- 1172-1182
- ISSN
- 0022-2836 (ISSN-L)
- PMC
- PMC3602375
- OpenAlex
- W2108241502
- Cited by
- 25
- References
- 48
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2014: 6 · 2013: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of Minnesota (T32 GM008244)
- National Institute on Drug Abuse (F30DA026310)
- National Institute of General Medical Sciences (T32GM008244, P50GM082250, P50GM081879, GM091743, GM-008244, GM081879, GM082250, P01GM091743)
- National Institute of Allergy and Infectious Diseases (R01AI064046, P01AI090935, P30AI027763)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- APOBEC3F, APOBEC3G, HIV-1 Vif, polyubiquitination, E3 ubiquitin ligase, antiviral restriction factors, DNA cytosine deaminase, proteasomal degradation
- MeSH terms
- APOBEC-3G Deaminase, Amino Acid Sequence, Binding Sites, Cytidine Deaminase, Humans, Lysine, Models, Biological, Models, Molecular, Mutation, Protein Binding, Mass Spectrometry, Blotting, Western, HIV-1, Protein Structure, Tertiary, Polyubiquitin, Cytosine Deaminase, vif Gene Products, Human Immunodeficiency Virus, Ubiquitination
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