Todd Yeates
Designed Protein Assemblies
One of the outstanding goals in bioengineering and nanotechnology is to design macromolecules that assemble into complex higher order structures. Considerable progress has been demonstrated in the last 20 years in designing DNA (and RNA) sequences to form interesting structures and materials. Progress in using proteins as the building blocks has been much more challenging, owing in part to the much greater complexity of the rules that govern the native structures of proteins. Nonetheless, Nature has achieved spectacular assemblies using protein molecules as her building blocks; virus shells, microtubules, and bacterial S-layers provide a few striking examples. One design approach we have explored involves fusing together two (or more) proteins, each of which has evolved in nature to form simple oligomers, such as homodimers and trimers. The resulting fusion protein inherits the symmetry properties of the two daughter components. Under the appropriate design conditions, the right combination of symmetry elements can lead to higher order assemblies, including cages, two-dimensional layers, and even three-dimensional crystals. These kinds of designed structures have been dubbed 'nanohedra'. Ongoing work is aimed at improving the design strategy. Numerous variations are being explored.
References:
- Wukovitz, S. W. and Yeates, T. O. 1995. Why Protein Crystals Favour Some Space Groups Over Others. Nature Structural Biology 2, 1062-1067.
- Padilla, J.E., Colovos, C., and Yeates, T.O. Nanohedra: 2001. Using Symmetry to Design Self-Assembling Protein Cages, Layers, Crystals and Filaments, Proc Natl Acad Sci USA, 98, 2217-2221.
- Serag, A.A., Altenbach, C., Gingery, M., Hubbell, W.L., and Yeates, T.O. 2002. Arrangement of Subunits and Ordering of -Strands in an Amyloid Sheet. Nature Struct. Biol. 9, 734-739.
- Yeates, T.O. and Padilla, J.P. 2002. Designing Supramolecular Protein Assemblies. 2002. Curr. Op. Struct. Biol. 12, 464-470.
- Banatao D.R., Cascio D., Crowley C.S., Fleissner M.R., Tienson H.L., and Yeates, T.O. (2006). An approach to crystallizing proteins by synthetic symmetrization. Proc. Natl.Acad. Sci. USA, 103, 16230-5.
