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ERC

ABEL Report Summary

Project ID: 340764
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Mid-Term Report Summary - ABEL (Alpha-helical Barrels: Exploring, Understanding and Exploiting a New Class of Protein Structure)

Whereas DNA and RNA largely store and pass on information in biology, proteins are often called the workhorses of biology as they do pretty much everything else. Despite their prominent and important roles, in terms of three-dimensional structures, proteins are limited in some senses. Specifically, nature appears to have used a relatively small number (<10,000 or so) of the many millions of the 3D structures that are believed to be possible. In other words, nature adapts proteins for different functions by appending different amino-acid chemistries onto otherwise similar frameworks. As a result, many theoretically possible proteins have not been observed in biology, and the signs are that they will not be found at all. These possible but as yet unused protein structures have been dubbed the dark matter of protein space. One of the objectives of this ERC grant is to explore one small part of this dark matter; namely, a class of rarely observed protein structures called the α-helical barrels.

A few years ago we made the serendipitous discovery of a simple α-helical barrel comprising 6 protein chains arranged in a bundle around a central cavity that was exposed at both ends. Our ERC application proposed to explore this structure and expand the number and type of α-helical barrels further using a combination of computation and experiment.

In the first half of the grant, we have managed to define a theoretical basis for designing α-helical barrels from first principles, and we have written computer programs to design new versions of these proteins rigorously. This has led to novel α-helical barrels with 5, 6 and 7 protein chains and internal cavities that increase in size accordingly. We have also been able to add chemical functions to these cavities and engineer entirely new proteins that are able to catalyse simple chemical reactions (a little like natural enzymes). We have shown that the cavities can bind a range of important natural small molecules. We can also assemble the barrels into new nanotube-like biomaterials by stacking them end of end. Finally, we have discovered that other α-helical barrels can be adapted from larger natural proteins and made to span biological membrane sending signals across them. These new proteins and discoveries could possibly lead to applications in the areas of biotechnology and synthetic biology.

Contact

Audrey Michael, (Deputy Faculty Financial Controller)
Tel.: +44 117 3317371
E-mail
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