The Woolfson (Chemistry and Biochemistry) and Clayden (Chemistry) groups have teamed up to make a new protein-like structure previously thought impossible. The work is reported in an article published in the journal Nature.
Most proteins are built from two structural building blocks – the alpha helix and the beta strand. These can be combined in different ways to generate an amazing gallery of 3D shapes that give natural proteins their many functions. Other structural building blocks do exist, but they are rare and thought not to be overly important in protein structure or function. One of these is called the 310-helix.
Uninhibited by the natural precedent for using alpha helices and the beta strands, and working between the two labs, Dr Prasun Kumar designed a protein-like molecule made solely from 310-helices. To do this, Prasun combined amino acids – the chemical units of proteins – that are found in natural proteins with others that are not. He made these designer proteins by chemical synthesis and showed that they formed bundles of pure 310-helices using X-ray crystallography.
The team now plans to probe this so-called “dark matter” of protein structure to explore chemistries and functions that go beyond those of natural proteins.
The work is funded by the BBSRC, supported by BrisSynBio, and involved a collaboration with Dr Neil Paterson at the Diamond Light Source.
- Kumar, P., Paterson, N.G., Clayden, J. et al. De novo design of discrete, stable 310-helix peptide assemblies. Nature (2022). https://doi.org/10.1038/s41586-022-04868-x