This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Fatty acid synthase (FAS) catalyzes the de novo synthesis of fatty acids and plays an essential role in embryogenesis and energy homeostasis. Inhibitors of FAS have the potential as treamtents for obesity, thereby reducing the risk for related cardiovascular diseases, and for cancer. The animal cytosolic FAS is a 272 kDa multienzyme polypeptide that requires dimerization for activity. Biochemical evidence suggests that FAS subunits assume a coiled, head-to-head architecture. This model has been substantiated by our subsequent structural characterization of single FAS particles by electron microscopy (EM) and is consistent with a recently published crystal structure. However in both structures the carboxyl-terminal domains were not identified, consistent with their known conformational mobility. We propose to continue our investigations of FAS by EM to unequivocally determine locations of these mobile carboxyl terminal domains and to investigate the conformations assumed by the FAS dimer at each step in fatty acid synthesis.
| Scapin, Giovanna; Dandey, Venkata P; Zhang, Zhening et al. (2018) Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis. Nature 556:122-125 |
| 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: |
| Geary, Cody; Chworos, Arkadiusz; Verzemnieks, Erik et al. (2017) Composing RNA Nanostructures from a Syntax of RNA Structural Modules. Nano Lett 17:7095-7101 |
| 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 |
| Razinkov, Ivan; Dandey, Venkat; Wei, Hui et al. (2016) A new method for vitrifying samples for cryoEM. J Struct Biol 195:190-198 |
| 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 |
| 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 |
Showing the most recent 10 out of 189 publications
