Solenoid proteins possess modular architectures comprising several repetitions of similar structural units. They are very abundant in natural organisms, since they are involved in many signal transduction pathways where they recognize one- and two-dimensional epitopes. The modular architecture supports this functionality, because the size and curvature of the paratope is easily adjusted by inserting or deleting entire structural units. These structural features are advantageous in vivo and can also be utilized for directed evolution experiments in vitro. Ankyrin and Armadillo repeats are two distinct structural units comprising two and three alpha helices that bind two and one-dimensional epitopes, respectively. Both types of repeats can be engineered in order to meet challenges in biochemical research.
Designed Ankyrin repeat proteins (DARPin) are 2D-binders that can be selected from combinatorial libraries to bind almost any target protein with high affinity. Additional advantageous properties, such as high expression yield and temperature stability, make them attractive for the development of crystallization aids, to overcome limitations in crystallogenesis for structural biology, molecular clamps and scaffold proteins. Using a stiff linker several DARPin domains can be combined into a polyvalent peptide chain that can recruit several targets into a stable complex.
Designed Armadillo repeat proteins (dArmRP) are 1D-binders that recognize flexible polypeptides. Models of dArmRPs suggest that dArmRPs and target peptides are anti-parallel and each Armadillo repeat recognizes two adjacent amino acids from the target. We utilize this unique architecture for the development a modular peptide recognition system, where the affinity of the binder can be easily adjusted to meet the requirements of the application.
In summary, dArmPRs and DARPins are two examples of engineered solenoid proteins with high potential for applications in basic research, clinical diagnostics and disease treatment.
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