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

Apolipoprotein B mRNA editing catalytic 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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Identification of domains in apobec-1 complementation factor required for RNA binding and apolipoprotein-B mRNA editing

RNA ◽

10.1017/s1355838202015649 ◽

2002 ◽

Vol 8 (1) ◽

pp. 69-82 ◽

Cited By ~ 50

Author(s):

ANURADHA MEHTA ◽

DONNA M. DRISCOLL

Keyword(s):

Apolipoprotein B ◽

Rna Binding ◽

Mrna Editing

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APOBEC-1, the catalytic subunit of the apolipoprotein B mRNA editing enzyme, is a mutifunctional cytidine deaminase with RNA binding activity

Gastroenterology ◽

10.1016/0016-5085(95)23872-7 ◽

1995 ◽

Vol 108 (4) ◽

pp. A303

Author(s):

A.J. MacGinnitie ◽

S. Anant ◽

C. Hadjiagapiou ◽

N.O. Davidson

Keyword(s):

Apolipoprotein B ◽

Rna Binding ◽

Cytidine Deaminase ◽

Binding Activity ◽

Catalytic Subunit ◽

Mrna Editing ◽

Editing Enzyme

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Mutagenesis of apobec-1, the Catalytic Subunit of the Mammalian Apolipoprotein B mRNA Editing Enzyme, Reveals Distinct Domains That Mediate Cytosine Nucleoside Deaminase, RNA Binding, and RNA Editing Activity

Journal of Biological Chemistry ◽

10.1074/jbc.270.24.14768 ◽

1995 ◽

Vol 270 (24) ◽

pp. 14768-14775 ◽

Cited By ~ 95

Author(s):

Andrew J. MacGinnitie ◽

Shrikant Anant ◽

Nicholas O. Davidson

Keyword(s):

Rna Editing ◽

Apolipoprotein B ◽

Rna Binding ◽

Catalytic Subunit ◽

Mrna Editing ◽

Editing Activity ◽

Editing Enzyme

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The editosome for cytidine to uridine mRNA editing has a native complexity of 27S: identification of intracellular domains containing active and inactive editing factors

Journal of Cell Science ◽

10.1242/jcs.115.5.1027 ◽

2002 ◽

Vol 115 (5) ◽

pp. 1027-1039 ◽

Cited By ~ 5

Author(s):

Mark P. Sowden ◽

Nazzareno Ballatori ◽

Karen L. de Mesy Jensen ◽

Lakesha Hamilton Reed ◽

Harold C. Smith

Keyword(s):

Apolipoprotein B ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Catalytic Subunit ◽

Cross Linking ◽

Primary Hepatocytes ◽

Mrna Editing ◽

Apob Mrna ◽

Rat Primary Hepatocytes

Apolipoprotein B mRNA cytidine to uridine editing requires the assembly of a multiprotein editosome comprised minimally of the catalytic subunit,apolipoprotein B mRNA editing catalytic subunit 1 (APOBEC-1), and an RNA-binding protein, APOBEC-1 complementation factor (ACF). A rat homolog has been cloned with 93.5% identity to human ACF (huACF). Peptide-specific antibodies prepared against huACF immunoprecipitated a rat protein of similar mass as huACF bound to apolipoprotein B (apoB) RNA in UV cross-linking reactions, thereby providing evidence that the p66, mooring sequence-selective, RNA-binding protein identified previously in rat liver by UV cross-linking and implicated in editosome assembly is a functional homolog of huACF. The rat protein (p66/ACF) was distributed in both the nucleus and cytoplasm of rat primary hepatocytes. Within a thin section, a significant amount of total cellular p66/ACF was cytoplasmic, with a concentration at the outer surface of the endoplasmic reticulum. Native APOBEC-1 co-fractionated with p66/ACF in the cytoplasm as 60S complexes. In the nucleus, the biological site of apoB mRNA editing, native p66/ACF, was localized to heterochromatin and fractionated with APOBEC-1 as 27S editosomes. When apoB mRNA editing was stimulated in rat primary hepatocytes with ethanol or insulin, the abundance of p66/ACF in the nucleus markedly increased. It is proposed that the heterogeneity in size of complexes containing editing factors is functionally significant and reflects functionally engaged editosomes in the nucleus and an inactive cytoplasmic pool of factors.

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