Functional repeat protein design – My ongoing projects

The ability to design large proteins with precise geometry that repeat  has led to numerous projects.

a. The ability to precisely adjust the shape of a protein scaffold from building blocks will make it very easy to quickly design de-novo protein-protein interfaces. In this project I have designed junction modules to connect the de-novo repeats. Design of junctions in naturally occurring LRR proteins has recently been done by Keunwan[  ], however, LRR are limited to beta-sheet interface interactions and do not offer the same degree of control as the designed helical repeat proteins.

b. Design of junctions between repeat proteins and parametrically designed bundles will allow us to make large protein cages and crystals. I am working with Una Nattermann and Yang Hsia on this project.

c. Controlled buildup of interdigitated proteins on Mica or Graphene has the potential to build exotic materials and with precisely controlled the shape. I am working with Harley Pyles and Professor Jim De Yoreo(Pacific Northwest National Laboratory – Material Science) on this project.

d. BAR proteins bend bilayers and recruit interaction partners trough poorly understood mechanisms[  ]. In this project I have designed a synthetic BAR proteins based on repeat proteins, my  collaborator Jihong Bai(Fred Hutchinson) will be using these synthetic BAR proteins to investigate how the BAR domain works.

e. I am developing de-novo protein tubes.  One potential of these tubes would be to order how carbon nanotubes assemble.

f. Embedding a heme, iron or copper in repeats should make electrically conductive protein wires. I am working with Anindya Roy on this.

Park, K., Shen, B. W., Parmeggiani, F., Huang, P.-S., Stoddard, B. L., & Baker, D. (2015). Control of repeat-protein curvature by computational protein design. Nature Structural & Molecular Biology, 22(2), 167–174.
Mim, C., Cui, H., Gawronski-Salerno, J. A., Frost, A., Lyman, E., Voth, G. A., & Unger, V. M. (2012). Structural basis of membrane bending by the N-BAR protein endophilin. Cell, 149(1), 137–145.