Tools of structural and computational biology will be used to uncover principles of biological recognition and assembly at the root of normal and pathological molecular complexes. The nature of the amyloid state of proteins, found in Alzheimer's and other neurodegenerative diseases, will be explored by x-ray diffraction and related methods. The primary goals will be learn the 3D structure of amyloid, which from preliminary experiments seems to be a dehydrated, hydrogen-bonded state. A second goal will be to understand the possible relationship of amyloid to the phenomenon of 3D domain swapping, found in other protein aggregates. In another line of work, computational methods will be extended for identifying the interacting networks of macromolecules in cells. Data from fully sequenced genomes will be basis of this work. Also structures of proteins will be determined that display interactions related to the general questions of recognition and assembly. One of these is glutamine synthetase, which may serve as an excellent target for a drug against tuberculosis.
| 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 |
| 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 |
| 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 |
| 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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