A5091061396- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- DNA Repair Mechanisms
- Acute Lymphoblastic Leukemia research
- Cytomegalovirus and herpesvirus research
- Acute Myeloid Leukemia Research
- DNA and Nucleic Acid Chemistry
- interferon and immune responses
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- Cardiomyopathy and Myosin Studies
- Bacteriophages and microbial interactions
- Nuclear Structure and Function
- Photosynthetic Processes and Mechanisms
- HIV-related health complications and treatments
- RNA Interference and Gene Delivery
- Invertebrate Immune Response Mechanisms
- Spectroscopy and Quantum Chemical Studies
Yale University
2020-2023
Whitney Museum of American Art
2020
James Madison University
2013-2015
Carrier (United States)
2014
Increasing evidence has suggested that the HIV-1 capsid enters nucleus in a largely assembled, intact form. However, not much is known about how cone-shaped interacts with nucleoporins (NUPs) nuclear pore for crossing complex. Here, we elucidate NUP153 binds by engaging assembled protein (CA) lattice. A bipartite motif containing both canonical and noncanonical interaction modules was identified at C-terminal tail region of NUP153. The cargo-targeting phenylalanine-glycine (FG) engaged CA...
From cellular deposition of the HIV-1 capsid to integration viral genome, constitutes a primary target variety host proteins that work either promote or inhibit infection. Successful progression infection depends on interactions between and factors involved in stability, transport, nuclear import, genome integration. The virus must also guard its reverse-transcribing inside from restriction bind suppress Understanding structure dynamics protein (CA) component assembled sheds light molecular...
SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage their triphosphorylated forms. Hence, inhibitors promising candidates sensitisation leukaemia cells analogue-based therapy. Here, we investigated effects cytosine analogue CNDAC, which has been proposed be a inhibitor, in context SAMHD1.
Elevated intracellular levels of dNTPs have been shown to be a biochemical marker cancer cells. Recently, series mutations in the multifunctional dNTP triphosphohydrolase (dNTPase), sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), reported various cancers. Here, we investigated structure functions SAMHD1 R366C/H mutants, found colon leukemia. Unlike many other cancer-specific mutations, R366 do not alter cellular enzyme. However, mutant proteins exhibit loss...
Summary The capsid of human immunodeficiency virus 1 (HIV-1) plays a pivotal role in viral nuclear import, but the mechanism by which core passages pore complex (NPC) is poorly understood. Here, we use DNA-origami mimics NPC, termed NuPODs (NucleoPorins Organized DNA), to reveal mechanistic underpinnings HIV-1 entry. We found that trimeric interface formed via three protein hexamers targeted triple-arginine (RRR) motif not canonical phenylalanine-glycine (FG) NUP153. As NUP153 located on...
SUMMARY Cyclic GMP-AMP synthase (cGAS) is a primary sensor of aberrant DNA that governs an innate immune signaling cascade, leading to the induction type-I interferon response. We have previously identified polyglutamine binding protein 1, PQBP1, as adaptor molecule required for cGAS-mediated response lentiviruses, including human immunodeficiency virus 1 (HIV-1), but dispensable recognition viruses. HIV-1- encoded synthesized single copy from its RNA genome, and subsequently integrated into...
Elevated intracellular dNTP level is a biochemical marker of cancer cells. Recently, series mutations in highly multi-functional dNTPase, SAMHD1, have been reported various cancers. Here we investigated the role SAMHD1 by characterizing cancer-specific mutations. R366C/H mutants, which were found two types, lost dNTPase activity and their X-ray structures demonstrate absence dGTP substrate active site, likely due to loss interaction with γ-phosphate substrate. The mutants failed reduce...
Summary Background SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage their triphosphorylated forms. Hence, inhibitors promising candidates sensitisation leukaemia cells analogue-based therapy. Here, we investigated effects cytosine analogue CNDAC, which has been proposed be a substrate, in context SAMHD1. Methods CNDAC was tested 13 acute myeloid (AML cell...