Modular assembly of a protein nanotriangle using orthogonally interacting coiled coils

• Main Authors: Park, Won Min (Contributor), Bedewy, Mostafa (Contributor), Berggren, Karl K. (Contributor), Keating, Amy E. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Massachusetts Institute of Technology. Research Laboratory of Electronics (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2017-12-11T18:13:54Z.
• Subjects: Article
• Online Access: Get fulltext

 Synthetic protein assemblies that adopt programmed shapes would support many applications in nanotechnology. We used a rational design approach that exploits the modularity of orthogonally interacting coiled coils to create a self-assembled protein nanotriangle. Coiled coils have frequently been used to construct nanoassemblies and materials, but rarely with successful prior specification of the resulting structure. We designed a heterotrimer from three pairs of heterodimeric coiled coils that mediate specific interactions while avoiding undesired crosstalk. Non-associating pairs of coiled-coil units were strategically fused to generate three chains that were predicted to preferentially form the heterotrimer, and a rational annealing proc ess led to the desired oligomer. Extensive biophysical characterization and modeling support the formation of a molecular triangle, which is a shape distinct from naturally occurring supramolecular nanostructures. Our approach can be extended to design more complex nanostructures using additional coiled-coil modules, other protein parts, or templated surfaces.