Viral infectivity factor (Vif) is an intrinsically disordered protein used by HIV-1 to hijack an immune cell’s natural defenses to prevent viral DNA degradation. Vif binds to an E3 ubiquitin ligase complex composed of Elongin B (EloB), Elongin C (EloC), CBF-ß and Cullin 5 (Cul5). In the ligase complex, Vif acts as a substrate binding protein for the APOBEC3 proteins (A3s), allowing for their ubiquitination and subsequent proteasomal degradation. Without A3s, HIV-1 can continue to spread to other cells. A3F is a member of the A3s family and is targeted by Vif for ubiquitination, but its binding mechanism is unknown. With the use of a computationally modeled E3 ubiquitin ligase complex bound to Vif and A3F, molecular dynamic simulations were used to identify the specific residue interactions in the Vif-A3F binding domain that stabilize the conformations sampled by the complex. Preliminary results show at least two interacting residue clusters in the binding domain per simulation. Binding domain residue patterns and their implications will be presented. Understanding the molecular basis of Vif’s affinity towards A3F will allow for the development of treatments that can target and interrupt Vif-A3F binding, rendering Vif and the rest of the virus useless.

Structural analysis of the Vif-A3F binding domain

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.