The ability to design and construct structures with atomic level precision
is one of the key goals of nanotechnology. Proteins offer an
attractive target for atomic design, as they can be synthesized chemically
or biologically, and can self-assemble. However the generalized
protein folding and design problem is unsolved. One approach to
simplifying the problem is to use a repetitive protein as a scaffold.
Repeat proteins are intrinsically modular, and their folding and structures
are better understood than large globular domains. Here, we
have developed a new class of synthetic repeat protein, based on
the pentapeptide repeat family of beta-solenoid proteins. We have
constructed length variants of the basic scaffold, and computationally
designed de novo loops projecting from the scaffold core. The
experimentally solved 3.56 ˚A resolution crystal structure of one designed
loop matches closely the designed hairpin structure, showing
the computational design of a backbone extension onto a synthetic
protein core without the use of backbone fragments from known
structures. Two other loop designs were not clearly resolved in the
crystal structures and one loop appeared to be in an incorrect conformation.
We have also shown that the repeat unit can accommodate
whole domain insertions by inserting a domain into one of the designed
loops.