The APOBECS's (A3G, ASF and possibly A3H) are cellular DNA cytosine deaminases that are key innate anti-viral agents, particularly in response to HIV-1. Although the structures of the catalytic domains of these important enzymes are beginning to be elucidated, the details of their specificities and interactions with other cellular and viral macromolecules still remains to be determined. In this proposal we are using a combination of crystallographic, molecular modelling, calorimetry, mass spectrometry and viral studies to characterize the domains of these various APOBEC3's, both intra-moleculariy within their domains and intermoleculariy with their interactions with HIV-1 Vif.

Public Health Relevance

When HIV infects the human body, many molecules attempt to prevent the virus from spreading. One such family of proteins are called the APOBEC3's. These proteins attempt to mutate the virus and make it less infectious. We are using molecular biophysical techniques to visualize these interactions in atomic detail, so that they can eventually be targeted for drug therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM091743-02
Application #
8375092
Study Section
Special Emphasis Panel (ZRG1-AARR-D)
Project Start
Project End
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$348,166
Indirect Cost
$91,463
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Silvas, Tania V; Hou, Shurong; Myint, Wazo et al. (2018) Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions. Sci Rep 8:7511
Pan, Yangang; Sun, Zhiqiang; Maiti, Atanu et al. (2017) Nanoscale Characterization of Interaction of APOBEC3G with RNA. Biochemistry 56:1473-1481
Richards, Christopher M; Li, Ming; Perkins, Angela L et al. (2017) Reassessing APOBEC3G Inhibition by HIV-1 Vif-Derived Peptides. J Mol Biol 429:88-96
Kouno, Takahide; Silvas, Tania V; Hilbert, Brendan J et al. (2017) Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. Nat Commun 8:15024
Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri et al. (2016) A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection. J Virol 90:474-85
Sharma, Ashwani; Haque, Farzin; Pi, Fengmei et al. (2016) Controllable self-assembly of RNA dendrimers. Nanomedicine 12:835-844
Lyubchenko, Yuri L; Shlyakhtenko, Luda S (2016) Imaging of DNA and Protein-DNA Complexes with Atomic Force Microscopy. Crit Rev Eukaryot Gene Expr 26:63-96
Shaban, Nadine M; Shi, Ke; Li, Ming et al. (2016) 1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure. J Mol Biol 428:2307-2316
Li, Hui; Zhang, Kaiming; Pi, Fengmei et al. (2016) Controllable Self-Assembly of RNA Tetrahedrons with Precise Shape and Size for Cancer Targeting. Adv Mater 28:7501-7
Prabhu, Ponnandy; Shandilya, Shivender M D; Britan-Rosich, Elena et al. (2016) Inhibition of APOBEC3G activity impedes double-stranded DNA repair. FEBS J 283:112-29

Showing the most recent 10 out of 83 publications