Proteins perform the most complex tasks in living organisms and are widely employed in medicine, biotechnology, chemistry and other areas. Designing of new, de novo protein structures is still very challenging since the large number of cooperative and long-range interactions determine the protein fold. However the ability of preparing new and smart polypeptide structures is of exceptional scientific and technological potential.
Members of the Department of biotechnology of the National institute of chemistry and Centre of excellence EN-FIST prof. Roman Jerala, dr. Helena Gradišar, dr. Iva Hafner-Bratkovič, PhD students Tibor Doles and Sabina Božič and coauthors prof. Sandi Klavžar, Damjan Vengust, dr. Alenka Mertelj, Ben Webb and prof. Andrej Šali from the Faculty of mathematics ad physics of the University of Ljubljana and University of Maribor, Jozef Stefan Institute and UCSF designed a polypeptide chain composed of defined order of modular peptides blocks that spontaneously self-assembles into the desired structure. The strategy was experimentally tested on the construction of a pyramid with a triangular base, a tetrahedron. A single polypeptide chain for tetrahedron was comprised of twelve coiled-coil-forming peptide segments interspersed with short flexible peptide linkers. In the resulting structure the polypeptide chain traverses each of the six edges exactly twice, forming coiled-coil dimers among the peptide pairs. The tetrahedral nanostructure was validated by a number of different methods, both biophysical (CD, DLS and fluorescence measurements) and by high resolution microscopy (TEM and AFM).
Researchers believe that new principle of protein-based nanostructure self-assembly could lead to the development of advanced materials for drug delivery, separation, catalysis as well as other applications, based on introduced functionalization.
The article was highlighted by Nature for its interest for the scientific as well as general public. After advanced online publication comments were published on the websites of Nature and Science magazines and Societies.
Report was published in the leading scientific journal from the field of chemical biology, Nature Chemical Biology.
Figure represents the principle of the designed modular polypeptide self-assembly. The single polypeptide chain is composed of twelve peptide segments concatenated with flexible peptide linkers and spontaneously self-assembles into the tetrahedral nanostructure. The order of the segments defines the final structure, underlying its application as a smart material. Transmission electron microscopy (TEM, right panel) revealed the pattern that corresponds to the different projections of a tetrahedron in accordance to the molecular model.