This Program Project represents an ongoing consortium of eight scientific investigators at UCLA, all of whom work together in using X-ray crystallography, NMR, EPR, or computational methods to analyze the structural basis for recognition. Three of the eight are Co-Principal Investigators and five are Participating Scientists (primarily for budgetary reasons). Specific problems to be addressed by the Project include: (1) How NarL and NarP, the response regulators of two-component bacterial signaling cascades, are activated for DNA binding by phosphorylation, and how they recognize and bind to their specific gene control sites. (2) How the base sequence and geometry of DNA dictate its binding to proteins and drugs, including inhibitors of the AIDS virus reverse transcriptase and side-by-side minor groove binding molecules. (3) How fully sequenced genomes an be used to identify interacting networks of macromolecules and previously uncharacterized protein assemblies. (4) How domain swapping influences protein aggregation, and whether it is involved in building the amyloid state. (5) Developing a new method for designing self-assembling proteins, and understanding how the design principles relate to biological assemblies, including cages and filaments. (6) Determination of the structure of eukaryotic glutamine synthetase as a step toward development of an anti-tuberculosis drug, and understanding of protein-ligand recognition. Although this list of projects by the three Co-PIs is diverse, the common thread through them all is that local structure controls interactions between macromolecules, and that recognition of one molecule by another is an essential step in the building of larger functional intermolecular assemblies. Space limitations prevent discussion of projects of Participating Scientists here, but their goals are similar.
| Katsir, Galit; Jarvis, Michael; Phillips, Martin et al. (2015) The Escherichia coli NarL receiver domain regulates transcription through promoter specific functions. BMC Microbiol 15:174 |
| Laganowsky, Arthur; Zhao, Minglei; Soriaga, Angela B et al. (2011) An approach to crystallizing proteins by metal-mediated synthetic symmetrization. Protein Sci 20:1876-90 |
| Yeates, Todd O; Crowley, Christopher S; Tanaka, Shiho (2010) Bacterial microcompartment organelles: protein shell structure and evolution. Annu Rev Biophys 39:185-205 |
| Boutz, Daniel R; Cascio, Duilio; Whitelegge, Julian et al. (2007) Discovery of a thermophilic protein complex stabilized by topologically interlinked chains. J Mol Biol 368:1332-44 |
| Banatao, D Rey; Cascio, Duilio; Crowley, Christopher S et al. (2006) An approach to crystallizing proteins by synthetic symmetrization. Proc Natl Acad Sci U S A 103:16230-5 |
| Norcross, Todd S; Yeates, Todd O (2006) A framework for describing topological frustration in models of protein folding. J Mol Biol 362:605-21 |
| Nelson, Rebecca; Eisenberg, David (2006) Recent atomic models of amyloid fibril structure. Curr Opin Struct Biol 16:260-5 |
| Laidman, Janel; Forse, G Jason; Yeates, Todd O (2006) Conformational change and assembly through edge beta strands in transthyretin and other amyloid proteins. Acc Chem Res 39:576-83 |
| Maris, Ann E; Kaczor-Grzeskowiak, Maria; Ma, Zhongcai et al. (2005) Primary and secondary modes of DNA recognition by the NarL two-component response regulator. Biochemistry 44:14538-52 |
| Nelson, Rebecca; Sawaya, Michael R; Balbirnie, Melinda et al. (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435:773-8 |
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