Computational design of symmetric eight and nine-bladed beta-propellers

Pseudo symmetric, repeat proteins are favoured targets for computational protein design as they allow for the creation of larger domains with limited amino acids by exploiting their symmetric and repeating nature. One of the most common pseudo symmetric, repeat domains is the β-propellers fold. In addition, they fulfil many functions from sugar binding to enzymatic and protein-protein interaction mediation, thus increasing the potential applications of the designed proteins. Each propeller is built from 4-stranded antiparallel β-sheets also known as a blade, repeated around a central axis. The number of blades differs from four to ten with seven and eight being the most common. The first successful computational protein design of a β-propeller was the 6-bladed Pizza protein. The RE3volutionary design method makes use of ancestral sequence reconstruction and symmetry based template construction methods incorporated in Rosetta. Each blade of the pizza protein possess the same amino acid sequence. When two or three repeats of this sequence are expressed, they self-assemble into the 6-bladed domain.