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 #
5P01GM091743-03
Application #
8433373
Study Section
Special Emphasis Panel (ZRG1-AARR-D)
Project Start
Project End
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
3
Fiscal Year
2013
Total Cost
$369,312
Indirect Cost
$109,738
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Shaban, Nadine M; Shi, Ke; Li, Ming et al. (2016) 1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure. J Mol Biol 428:2307-16
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
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
Sharma, Ashwani; Haque, Farzin; Pi, Fengmei et al. (2016) Controllable self-assembly of RNA dendrimers. Nanomedicine 12:835-44
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
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
Li, Jinhui; Barylko, Barbara; Eichorst, John P et al. (2016) Association of Endophilin B1 with Cytoplasmic Vesicles. Biophys J 111:565-76
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
Kouno, Takahide; Luengas, Elizabeth M; Shigematsu, Megumi et al. (2015) Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G. Nat Struct Mol Biol 22:485-91
Shlyakhtenko, Luda S; Dutta, Samrat; Banga, Jaspreet et al. (2015) APOBEC3G Interacts with ssDNA by Two Modes: AFM Studies. Sci Rep 5:15648

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