Design of Polypeptide Topological Folds Based on Concatenated Coiled-coil Modules
Presented by Dr. Ajasja LJUBETIč, Prof. Tomaž PISANSKI
Type: Oral presentation
Proteins as the central molecules of life fold into versatile compact tertiary structures defined by a large number of cooperative weak long range interactions, which are very difficult to predict and even more to design. DNA-based nanostructures can represent an inspiration for the design of new protein folds. In comparison to DNA, polypeptide coiled-coil dimers can form both parallel and antiparallel dimers. Additionally we can design coiled-coil dimers that are orthogonal. The challenge was to design an Eulerian polypeptide trail where each of the edges of a tetrahedron is crossed exactly twice. We designed a new type of protein folds using orthogonal coiled-coil modules to guide the assembly of the topological protein folds. In this case the protein fold is defined by the precisely defined sequential order of concatenated orthogonal coiled-coil dimer forming segments, which can self-assemble into protein polyhedral cage. This principle was first demonstrated on the construction of a nanoscale protein tetrahedron, composed of a single polypeptide chain composed of 12 coiled-coil forming segments (Gradišar et al., NatChemBiol 2013). This represents a new platform of structural scaffold formation that could be extended to other polyhedra and could be used for different applications. This is a joint work with Helena Gradišar, Vid Kočar, Karen Butina, Igor Drobnak, Sabina Božič Abram, Tibor Doles, Nino Bašić, and Roman Jerala.