Insights into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Apr 3

PMID 33802945

Citations 10

Authors

Xiaojiang S Chen

Affiliations

Soon will be listed here.

Abstract

lipoprotein mRNA diting atalytic polypeptide-like (APOBEC) proteins belong to a family of deaminase proteins that can catalyze the deamination of cytosine to uracil on single-stranded DNA or/and RNA. APOBEC proteins are involved in diverse biological functions, including adaptive and innate immunity, which are critical for restricting viral infection and endogenous retroelements. Dysregulation of their functions can cause undesired genomic mutations and RNA modification, leading to various associated diseases, such as hyper-IgM syndrome and cancer. This review focuses on the structural and biochemical data on the multimerization status of individual APOBECs and the associated functional implications. Many APOBECs form various multimeric complexes, and multimerization is an important way to regulate functions for some of these proteins at several levels, such as deaminase activity, protein stability, subcellular localization, protein storage and activation, virion packaging, and antiviral activity. The multimerization of some APOBECs is more complicated than others, due to the associated complex RNA binding modes.

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References

Fossat N, Tourle K, Radziewic T, Barratt K, Liebhold D, Studdert J . C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47. EMBO Rep. 2014; 15(8):903-10. PMC: 4197048. DOI: 10.15252/embr.201438450. View

Chiu Y, Witkowska H, Hall S, Santiago M, Soros V, Esnault C . High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition. Proc Natl Acad Sci U S A. 2006; 103(42):15588-93. PMC: 1592537. DOI: 10.1073/pnas.0604524103. View

Sowden M, Ballatori N, Jensen K, Reed L, Smith H . The editosome for cytidine to uridine mRNA editing has a native complexity of 27S: identification of intracellular domains containing active and inactive editing factors. J Cell Sci. 2002; 115(Pt 5):1027-39. DOI: 10.1242/jcs.115.5.1027. View

Yeap L, Hwang J, Du Z, Meyers R, Meng F, Jakubauskaite A . Sequence-Intrinsic Mechanisms that Target AID Mutational Outcomes on Antibody Genes. Cell. 2015; 163(5):1124-1137. PMC: 4751889. DOI: 10.1016/j.cell.2015.10.042. View

Teng B, Burant C, Davidson N . Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science. 1993; 260(5115):1816-9. DOI: 10.1126/science.8511591. View

Harjes E, Gross P, Chen K, Lu Y, Shindo K, Nowarski R . An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model. J Mol Biol. 2009; 389(5):819-32. PMC: 2700007. DOI: 10.1016/j.jmb.2009.04.031. View

Muckenfuss H, Hamdorf M, Held U, Perkovic M, Lower J, Cichutek K . APOBEC3 proteins inhibit human LINE-1 retrotransposition. J Biol Chem. 2006; 281(31):22161-22172. DOI: 10.1074/jbc.M601716200. View

Horn A, Klawitter S, Held U, Berger A, Vasudevan A, Bock A . Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity. Nucleic Acids Res. 2013; 42(1):396-416. PMC: 3874205. DOI: 10.1093/nar/gkt898. View

Yu Q, Chen D, Konig R, Mariani R, Unutmaz D, Landau N . APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem. 2004; 279(51):53379-86. DOI: 10.1074/jbc.M408802200. View

10.

Sharma S, Baysal B . Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G. PeerJ. 2017; 5:e4136. PMC: 5723131. DOI: 10.7717/peerj.4136. View

11.

McLaughlin Jr R, Gable J, Wittkopp C, Emerman M, Malik H . Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution. Mol Biol Evol. 2016; 33(8):1889-901. PMC: 5010000. DOI: 10.1093/molbev/msw070. View

12.

Jalili P, Bowen D, Langenbucher A, Park S, Aguirre K, Corcoran R . Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots. Nat Commun. 2020; 11(1):2971. PMC: 7293259. DOI: 10.1038/s41467-020-16802-8. View

13.

Methot S, Litzler L, Subramani P, Eranki A, Fifield H, Patenaude A . A licensing step links AID to transcription elongation for mutagenesis in B cells. Nat Commun. 2018; 9(1):1248. PMC: 5871760. DOI: 10.1038/s41467-018-03387-6. View

14.

Suspene R, Aynaud M, Koch S, Pasdeloup D, Labetoulle M, Gaertner B . Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo. J Virol. 2011; 85(15):7594-602. PMC: 3147940. DOI: 10.1128/JVI.00290-11. View

15.

Blanc V, Sessa K, Kennedy S, Luo J, Davidson N . Apobec-1 complementation factor modulates liver regeneration by post-transcriptional regulation of interleukin-6 mRNA stability. J Biol Chem. 2010; 285(25):19184-92. PMC: 2885197. DOI: 10.1074/jbc.M110.115147. View

16.

Nakashima M, Ode H, Kawamura T, Kitamura S, Naganawa Y, Awazu H . Structural Insights into HIV-1 Vif-APOBEC3F Interaction. J Virol. 2015; 90(2):1034-47. PMC: 4702671. DOI: 10.1128/JVI.02369-15. View

17.

Ahasan M, Wakae K, Wang Z, Kitamura K, Liu G, Koura M . APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity. Biochem Biophys Res Commun. 2015; 457(3):295-9. DOI: 10.1016/j.bbrc.2014.12.103. View

18.

Siu K, Sultana A, Azimi F, Lee J . Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F. Nat Commun. 2013; 4:2593. PMC: 4956467. DOI: 10.1038/ncomms3593. View

19.

Sheehy A, Gaddis N, Choi J, Malim M . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002; 418(6898):646-50. DOI: 10.1038/nature00939. View

20.

Honjo T, Nagaoka H, Shinkura R, Muramatsu M . AID to overcome the limitations of genomic information. Nat Immunol. 2005; 6(7):655-61. DOI: 10.1038/ni1218. View