Research Press Release

Self-assembling protein origami

Nature Biotechnology

October 17, 2017

A method to build nanoscale protein cages in various polyhedral shapes from a single polypeptide is reported in a paper published online this week in Nature Biotechnology. The study shows that the cages self-assemble in solution, as well as in bacteria, mammalian cells and living mice. A diverse array of potential applications is envisaged, from drug delivery and vaccination to bottom-up fabrication of new materials that incorporate amino-acid functionality.

The past decade has witnessed rapid advances in methods for making molecular structures out of DNA by carefully choosing DNA sequences that bind to each other in a predictable way and fold into a desired shape. Roman Jerala and colleagues extend this approach - called DNA origami, after the Japanese art of paper folding - to proteins.

The authors show that ‘coiled coils’ containing two intertwined helical strands - a form that occurs naturally in proteins - can be used as modular building blocks to construct protein cages in the shape of a tetrahedron, a four-sided pyramid and a triangular prism. They show that the proteins are soluble in aqueous solution, self-assemble inside or outside cells, and appear biocompatible in mice. By testing various parameters of the system, such as the charge of the coiled coils and the presence of a 'cap' at their ends, the authors develop a toolbox of coiled-coil building blocks and a semi-automated computational pipeline to facilitate the design of protein origami in any polyhedral shape.

DOI:10.1038/nbt.3994 | Original article

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