Abstract

PROJECT 1 - IN (STROUD. PROJECT LEADER)Our goal is to understand the mechanism of HIV-1 integration mediated by integrase (IN), in thecontext of pre-integration complexes (PICs) that provide the targets for anti-IN drugs. The components ofPICs, and interactions with viral and cellular proteins will be defined. Our plan builds on our 1.6 A resolutionstructure of the isolated core domain (IN52'210), our 2.6 A structure of the two-domain catalytic core plus Cterminaldomain (IN52'288), and our exclusive ability to prepare homogeneous thiol-linked IN-DNA complexes.We will further analyze the crystal structure of IN without and with its natural substrate, the viral att site andtarget DNA, and use that knowledge to determine the mechanisms of anti-IN therapeutics.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
1P50GM082250-01
Application #
7480051
Study Section
Special Emphasis Panel (ZRG1-AARR-A (40))
Project Start
2007-09-01
Project End
2012-07-31
Budget Start
2007-09-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$421,694
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Eckhardt, Manon; Zhang, Wei; Gross, Andrew M et al. (2018) Multiple Routes to Oncogenesis Are Promoted by the Human Papillomavirus-Host Protein Network. Cancer Discov 8:1474-1489
Masand, Ruchi; Paulo, Esther; Wu, Dongmei et al. (2018) Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits. Cell Metab 27:616-629.e4
Binning, Jennifer M; Smith, Amber M; Hultquist, Judd F et al. (2018) Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors. PLoS Pathog 14:e1006830
Morris, Kyle L; Buffalo, Cosmo Z; Stürzel, Christina M et al. (2018) HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation. Cell 174:659-671.e14
Chen, Si-Han; Jang, Gwendolyn M; Hüttenhain, Ruth et al. (2018) CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling. EMBO J 37:
Leoz, Marie; Kukanja, Petra; Luo, Zeping et al. (2018) HEXIM1-Tat chimera inhibits HIV-1 replication. PLoS Pathog 14:e1007402
Cheng, Yifan (2018) Single-particle cryo-EM-How did it get here and where will it go. Science 361:876-880
Roth, Theodore L; Puig-Saus, Cristina; Yu, Ruby et al. (2018) Reprogramming human T cell function and specificity with non-viral genome targeting. Nature 559:405-409
Ferdin, Jana; Gori?ar, Katja; Dolžan, Vita et al. (2018) Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA. PLoS One 13:e0191613
Cheng, Yifan (2018) Membrane protein structural biology in the era of single particle cryo-EM. Curr Opin Struct Biol 52:58-63

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