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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AARR-A (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Ivry, Sam L; Meyer, Nicole O; Winter, Michael B et al. (2018) Global substrate specificity profiling of post-translational modifying enzymes. Protein Sci 27:584-594
Cary, Daniele C; Peterlin, B Matija (2018) Procyanidin trimer C1 reactivates latent HIV as a triple combination therapy with kansui and JQ1. PLoS One 13:e0208055
Palovcak, Eugene; Wang, Feng; Zheng, Shawn Q et al. (2018) A simple and robust procedure for preparing graphene-oxide cryo-EM grids. J Struct Biol 204:80-84
Tambe, Akshay; East-Seletsky, Alexandra; Knott, Gavin J et al. (2018) RNA Binding and HEPN-Nuclease Activation Are Decoupled in CRISPR-Cas13a. Cell Rep 24:1025-1036
Paulo, Esther; Wu, Dongmei; Wang, Yangmeng et al. (2018) Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis. Sci Rep 8:11001
Faust, Tyler B; Li, Yang; Bacon, Curtis W et al. (2018) The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation. Elife 7:
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; St├╝rzel, Christina M et al. (2018) HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation. Cell 174:659-671.e14

Showing the most recent 10 out of 199 publications