A general strategy will be explored for designing novel proteins that self- assemble into large symmetrical structures, including nanoparticle cages, filaments, layers, and porous crystalline materials. The method makes use of natural oligomeric proteins, genetically fused in precise arrangement. The present proposal is to fully explore this new area of symmetric protein design we will validate the method and test its limitations by designing and experimentally characterizing a series of assemblies with a wide range of architectures. Beyond the potential future applications in materials science, the principles underlying these assemblies will be used to illuminate and guide experiments on some natural protein assemblies. Genomic studies will uncover potentially uncharacterized protein complexes that have evolved by acquiring multiple oligomerization domains. The quaternary structure and symmetry of interesting candidates will be investigated by biophysical and crystallographic methods. Finally, fiber forming proteins, such as the amyloid protein transthyretin, will be studied by chemical cross-linking and EPR methods to see what role symmetry may play in filamentous assemblies.
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 |
Showing the most recent 10 out of 127 publications