# Structural Studies of APOBEC-Vif Complexes

> **NIH NIH R56** · UNIVERSITY OF MINNESOTA · 2020 · $383,631

## Abstract

The APOBEC3 antiviral factors are single-stranded DNA cytosine deaminases that potently restrict HIV
replication by hypermutation of viral cDNA replication intermediates. Several of these enzymes also have the
capacity to restrict virus replication by a deaminase-independent mechanism that involves direct binding to viral
RNA genomes. HIV counteracts this threat by encoding an accessory protein called Vif, which hijacks cellular
CBFβ and an E3-ligase complex to bind up to five APOBEC3s and target them for proteasomal degradation
(APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H). Despite considerable progress over
the past two decades, a comprehensive biochemical and structural understanding of these APOBEC3-Vif
complexes is still lacking. Here, we propose to fill these gaps in knowledge through two specific aims. In Aim 1
we will determine structures of Vif-CBFβ-E3 ubiquitin ligase complexes. In Aim 2 we will determine the atomic
details of multiple A3-Vif complexes using x-ray crystallography and/or single-particle cryo-EM. These structures
will demonstrate the mechanisms used by Vif to interact with multiple host factors and protect the virus from
APOBEC3-mediated restriction. A detailed biochemical and structural understanding of these host-pathogen
interactions is anticipated to inform the development of new antiviral strategies such as therapeutic targeting of
conserved structural motifs.

## Key facts

- **NIH application ID:** 10239277
- **Project number:** 1R56AI150402-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nadine M. Shaban
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,631
- **Award type:** 1
- **Project period:** 2020-09-04 → 2022-04-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239277

## Citation

> US National Institutes of Health, RePORTER application 10239277, Structural Studies of APOBEC-Vif Complexes (1R56AI150402-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239277. Licensed CC0.

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