Protein Tinker Toys: Self-Assembling Catalytic Biomaterials
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Protein complexes do nature’s tough jobs
Nature uses protein complexes containing multiple different proteins which operate synergistically to accomplish difficult tasks, such as breaking down cellulose into glucose. Previous attempts to create synthetic protein complexes have had limited success, but now, researchers at SUNY Upstate Medical University have developed novel protein constructs that used to build synthetic protein complexes similar to those found in nature.
Building synthetic protein complexes
Upstate uses a technique it calls domain swapping to create the building blocks of its synthetic protein complexes. The amino acid chains of many proteins are folded such that separate portions of the protein interact structurally almost as if they were actually two separate proteins, fitting together like two puzzle pieces. Cleaving the protein separates these two interacting portions into complementary protein fragments that will interact structurally and bind if brought together. Upstate creates synthetic domain swapping modules (DSMs) by placing a lever protein between the two complementary portions of what we call the assembler protein to hold them apart and keep them from interacting.
Attaching a DSM to one or both ends of a target protein of interest creates a protein construct that will predictably self-assemble with another protein construct incorporating a complementary DSM to form a protein complex incorporating the target proteins of both constructs. By using various DSMs, a set of constructs can be designed that will, when mixed, self-assemble into a protein complex having a pre-determined structure, which can be simple (chains) or complex (2-D meshes or 3-D lattices). It is due to the extreme flexibility with which Upstate’s protein complexes can be used to build custom complexes that we call them protein tinker toys; almost any structure is possible.
The protein tinker toys Upstate has developed can be used for a broad range of applications, including:
• Drug delivery. DSM-generated hydrogels can be designed as inert matrices for encapsulating drugs, or to actively release a drug over time as the gel breaks down. Proteins that bind the gel to a specific cellular receptor can be added.