APOBEC3G

1. 본문

APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic subunit 3G) is a human enzyme that plays a significant role in innate antiviral immunity. Here's a breakdown of what APOBEC3G is and what it does:
Function:

• DNA Editing Enzyme: APOBEC3G is a cytidine deaminase, meaning it catalyzes the deamination of cytidine to uridine in single-stranded DNA.
• Antiviral Activity: It acts as an inhibitor of retrovirus replication (like HIV) and retrotransposon mobility. It achieves this through both deaminase-dependent and -independent mechanisms.
• Mutation Induction: During reverse transcription in retroviruses, APOBEC3G can deaminate viral cDNA cytosines (C) to uracils (U). This leads to guanine (G) to adenine (A) mutations in the viral DNA, which can be lethal to the virus.
• Pre-integration blocking: Even without causing mutations, APOBEC3G can interfere with the integration of the viral DNA into the host cell's genome, further blocking viral replication.

How it Works Against HIV:1. APOBEC3G gets incorporated into HIV-1 particles.

2. When the virus infects a new cell and starts reverse transcription (converting its RNA to DNA), APOBEC3G acts on the single-stranded viral DNA.

3. It converts cytosines to uracils in the DNA.

4. This results in G-to-A mutations in the viral genome, disrupting viral replication.
Viral Counteraction:

• HIV has evolved a protein called Viral infectivity factor (Vif) to counteract APOBEC3G.
• Vif binds to APOBEC3G, triggering its ubiquitination and degradation by the cell's proteasome, preventing APOBEC3G from being packaged with virus and interfering APOBEC3G's functions.
• Foamy viruses utilize their Bet protein to counter APOBEC3G by decreasing the cytoplasmic solubility of the enzyme.

Other Key Points:

• APOBEC Superfamily: APOBEC3G belongs to the larger APOBEC superfamily of proteins, all involved in editing DNA and/or RNA.
• Gene Location: The *APOBEC3G* gene is located on chromosome 22 in humans. It's part of a cluster of related genes thought to have arisen from gene duplication.
• Isoforms: APOBEC3G has multiple isoforms that result from the alternative splicing.
• Molecular Weight: The calculated molecular weight is approximately 46 kDa.
• Sublethal Mutagenesis: Besides causing lethal mutations, it's also suggested that APOBEC3G can introduce sublethal mutations, potentially contributing to HIV-1 genetic variation.