Researchers Make “Impossible” Nano-sized Protein Cages with The Help Of Gold

An international group of researchers centres at the Malopolska Centre of Biotechnology, Jagiellonian University in Poland have produce a super-stable artificial protein ball that apparently defies the rules of geometry and which may have applications in materials science and medicine.

Every role playing gamer knows that there are restrictions governing the shape of dice; try to make a six-sided die by replacing the square faces with triangles and you will be left with something horribly distorted and certainly not fair. The reason for this is that there are geometrical rules describing what kind of shapes are allowed to be the faces of die-like shapes, so-called regular convex polyhedra. In nature too such shapes are common at the microscopic level. Usually made from many proteins and having a hollow interior, these nanoscale objects are known as protein cages and they carry out a variety of important tasks. The most famous example are viruses where the cage carries viral genetic material into host cells.

Researchers are interested in making artificial protein cages in the hope that they may be able to design them to have useful properties not found in nature. There are two challenges to achieving this goal. The first is the geometry problem: some proteins may have great potential utility but seem to be ruled out because they have the wrong shape to assemble into cages. The second problem is complexity: in nature the many proteins that form a protein cage are held together by a complex network of chemical bonds and these are very difficult to predict and simulate.

In the new work, headed by Professor Jonathan Heddle at the Bionanoscience and Biochemistry Laboratory Malopolska Centre of Biotechnology, Jagiellonian University and funded largely by Poland’s National Science Centre, researchers found a way to solve both of these problems. “We were able to replace the complex interactions between proteins with a simple ‘staple’ consisting of a single gold atom.” explains Professor Heddle the senior author of the research. "This simplifies the design problem and allows us to imbue the cages with new properties such as assembly and disassembly on demand.” The research has also found a way to get around the geometrical problem: “The building block of a protein cage is an 11-sided shape.” says Heddle “Theoretically this should not be able to form the faces of a regular convex polyhedron." However the research has found that while this is mathematically true, some so-called “impossible shapes” can assemble into cages which are so close to being regular that the errors are not noticeable. “What this means is that we can now use proteins which we previously would not have considered because they are theoretically unable to form cages." says Heddle. 

The potential implications of the work a far-reaching. "What we, together with our collaborators have found, is simply the first step." notes Heddle, who hopes that the work can be expanded further to produce cages with new structures and new capabilities and also investigated for potential applications particularly in drug delivery.

The research appears in the article “An ultra-stable gold-coordinated protein cage displaying reversible assembly” in the May16^th issue of Nature.  http://dx.doi.org/10.1038/s41586-019-1185-4