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HIV1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold (2013). PNAS 110:E123-131
CBFβ stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression (2013). Mol. Cell, 49: 632-44
Global landscape of HIV-human protein complexes (2012).Nature, 481, p. 365-70
Vif hijacks CBFbeta to degrade APOBEC3G and promote HIV-1 infection (2012). Nature, 481, p. 371-5
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HARC Center Mission:
The HARC Center is an interdisciplinary research center aimed at creating a comprehensive structural picture of interactions between HIV viral proteins and intracellular host molecules at early stages in the viral lifecycle. High-resolution structures of such complexes offer the potential for novel targeted drug design strategies in the treatment of AIDS.
Throughout the HIV life cycle, viral-host complexes play an integral role in the biology of the virus. The HARC Center focuses on a subset of complexes involved in hijacking host machinery for transcription, export and trafficking of nucleic acids, and degradation and evasion of anti-viral restriction factors. Our major projects involve HIV accessory and regulatory proteins (e.g. Rev, Tat and Vif) that interact with the host machinery and viral nucleic acids to affect key functions. We are also utilizing a proteomics approach to generate a comprehensive map of high quality, validated interactions for these proteins and others in the HIV genome.
The Center is comprised of researchers from ten different laboratories at UCSF and Berkeley, and is one of three Specialized Centers for Determination of Structures and HIV-host Complexes funded by the NIH AIDS-Related Structural Biology Program at the National Institute of General Medical Sciences (NIGMS). Members of the HARC Center provide expertise within a comprehensive range of biochemical, molecular biological and structural methods, including mass spectroscopy, x-ray crystallography, NMR and cryo-electron microscopy.
In conjunction with its research activities, the Center makes new methodologies, tools and databases available to the research community at large, and is active in creating new collaborations with outside investigators.
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