Modular assembly of a protein nanotriangle using orthogonally interacting coiled coils

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 use...

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Bibliographic Details
Main Authors: Park, Won Min, Bedewy, Mostafa, Berggren, Karl K., Keating, Amy E.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: Nature Publishing Group 2017
Online Access:http://hdl.handle.net/1721.1/112685
https://orcid.org/0000-0002-6076-6353
https://orcid.org/0000-0003-4182-7533
https://orcid.org/0000-0001-7453-9031
https://orcid.org/0000-0003-4074-8980
Description
Summary: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.