This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Protein ubiquitination is a post-translational modification widely utilized in eukaryotic regulation. The best known function of ubiquitin is to mark proteins for proteasomal degradation. This and other functions require first activation of ubiquitin by the E1 enzyme, followed by binding to one of ~40 E2 conjugases. Finally, specificity of ubiquitination is conferred by E3 ligases. The activity of most E3s is specified by a RING domain, which binds to the E2~ubiquitin conjugate and activates release of ubiquitin to attack a lysine residue in a substrate protein, bound to a separate domain in the E3. Over 600 human genes encode E3s, consistent with these enzymes'known functions in the control of many cellular processes, and with their involvement in multiple diseases. Solving the structure of this E3 complex will help understand its function and should contribute to the understanding of the mechanism of action of E3s in general. The more detailed our understanding of basic principles underlying E3 function becomes, the more accurately we will be able to understand how they are regulated and what effects disease mutations have on activity. Last but not least, by understanding of the mechanism of action of E3s we should be able to design E3-targeting small molecule inhibitors and interpret the effects of such drugs.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR017573-10
Application #
8362470
Study Section
Special Emphasis Panel (ZRG1-CB-B (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$25,707
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kulczyk, Arkadiusz W; Moeller, Arne; Meyer, Peter et al. (2017) Cryo-EM structure of the replisome reveals multiple interactions coordinating DNA synthesis. Proc Natl Acad Sci U S A 114:E1848-E1856
Sherman, Michael B; Kakani, Kishore; Rochon, D'Ann et al. (2017) Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission. J Virol 91:
Short, James R; Speir, Jeffrey A; Gopal, Radhika et al. (2016) Role of Mitochondrial Membrane Spherules in Flock House Virus Replication. J Virol 90:3676-83
Razinkov, Ivan; Dandey, Venkat; Wei, Hui et al. (2016) A new method for vitrifying samples for cryoEM. J Struct Biol 195:190-198
Guenaga, Javier; de Val, Natalia; Tran, Karen et al. (2015) Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. PLoS Pathog 11:e1004570
McCullough, John; Clippinger, Amy K; Talledge, Nathaniel et al. (2015) Structure and membrane remodeling activity of ESCRT-III helical polymers. Science 350:1548-51
McNulty, Reginald; Lokareddy, Ravi Kumar; Roy, Ankoor et al. (2015) Architecture of the Complex Formed by Large and Small Terminase Subunits from Bacteriophage P22. J Mol Biol 427:3285-3299
Lee, Jeong Hyun; Leaman, Daniel P; Kim, Arthur S et al. (2015) Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike. Nat Commun 6:8167
Derking, Ronald; Ozorowski, Gabriel; Sliepen, Kwinten et al. (2015) Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLoS Pathog 11:e1004767
Grover, Rajesh K; Zhu, Xueyong; Nieusma, Travis et al. (2014) A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union. Science 343:656-661

Showing the most recent 10 out of 187 publications