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 #
1P01GM091743-01A1
Application #
8078336
Study Section
Special Emphasis Panel (ZRG1-AARR-D (40))
Project Start
2011-03-01
Project End
2015-12-31
Budget Start
2011-03-01
Budget End
2011-12-31
Support Year
1
Fiscal Year
2011
Total Cost
$350,086
Indirect Cost
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
Khisamutdinov, Emil F; Jasinski, Daniel L; Li, Hui et al. (2016) Fabrication of RNA 3D Nanoprisms for Loading and Protection of Small RNAs and Model Drugs. Adv Mater 28:10079-10087
Li, Jinhui; Barylko, Barbara; Eichorst, John P et al. (2016) Association of Endophilin B1 with Cytoplasmic Vesicles. Biophys J 111:565-576
Shlyakhtenko, Luda S; Dutta, Samrat; Li, Ming et al. (2016) Single-Molecule Force Spectroscopy Studies of APOBEC3A-Single-Stranded DNA Complexes. Biochemistry 55:3102-6
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

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