Stroud, Robert M.

Abstract

PROJECT 1 - IN (STROUD. PROJECT LEADER) Our goal is to understand the mechanism of HIV-1 integration mediated by integrase (IN), in the context of pre-integration complexes (PICs) that provide the targets for anti-IN drugs. The components of PICs, and interactions with viral and cellular proteins will be defined. Our plan builds on our 1.6 A resolution structure of the isolated core domain (IN52""""""""210), our 2.6 A structure of the two-domain catalytic core plus Cterminal domain (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 and target 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 #: 5P50GM082250-04
• Application #: 8119495
• Study Section: Special Emphasis Panel (ZRG1)
• Budget Start: 2010-08-01
• Budget End: 2011-07-31
• Support Year: 4
• Fiscal Year: 2010
• Total Cost: $397,398

Institution

• Name: University of California San Francisco
• 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