APOBEC3G

Enzyme involved in the immune response to viral infections

Overview

APOBEC3G is a member of the APOBEC family of cytidine deaminases, which are enzymes that play a crucial role in the innate immune response to viral infections. APOBEC3G is particularly known for its ability to inhibit the replication of HIV and other retroviruses by inducing hypermutation in the viral genome.

Structure and Function

APOBEC3G is a single-stranded DNA cytidine deaminase that catalyzes the deamination of cytidine to uridine. This enzymatic activity results in the introduction of mutations in the viral DNA during reverse transcription, which can lead to the degradation of the viral genome or the production of non-functional viral proteins.

The enzyme is composed of two zinc-coordinating domains, each containing a characteristic zinc finger motif. These domains are essential for the catalytic activity and substrate binding of APOBEC3G. The N-terminal domain is primarily responsible for RNA binding, while the C-terminal domain contains the active site for deamination.

Role in HIV Restriction

APOBEC3G is a potent inhibitor of HIV replication. It is packaged into budding virions in the absence of the viral protein Vif (virion infectivity factor). Once inside the target cell, APOBEC3G deaminates cytidines in the negative strand of the viral DNA during reverse transcription, leading to G-to-A hypermutations in the positive strand. These mutations can render the virus non-infectious.

Diagram of an HIV virion, showing the incorporation of APOBEC3G in the absence of Vif.

However, HIV has evolved a counter-defense mechanism through the Vif protein, which binds to APOBEC3G and targets it for ubiquitination and subsequent degradation by the proteasome. This prevents APOBEC3G from being incorporated into new virions, allowing the virus to replicate efficiently.

Clinical Implications

Understanding the interaction between APOBEC3G and HIV has significant implications for the development of new therapeutic strategies. Inhibitors of the Vif-APOBEC3G interaction could potentially restore the antiviral activity of APOBEC3G, providing a novel approach to HIV treatment.

Additionally, the role of APOBEC3G in inducing mutations has been implicated in cancer development. The enzyme's activity can lead to mutations in host DNA, contributing to oncogenesis in certain contexts.

Related pages

• APOBEC family
• HIV
• Cytidine deaminase
• Innate immune system