Engineering nanoscale order into a designed protein fiber

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 26; pp. 10853 - 10858
• Main Authors: Papapostolou, David, Smith, Andrew M, Atkins, Edward D.T, Oliver, Seb J, Ryadnov, Maxim G, Serpell, Louise C, Woolfson, Derek N
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 26.06.2007; National Acad Sciences
• Subjects: Biochemistry; Biocompatible Materials - chemical synthesis; Biological Sciences; Biomimetic Materials - chemical synthesis; Biophysics; Design; Design engineering; Diffraction patterns; Modeling; Mutation; Nanostructures; Nanotechnology; Peptides; Peptides - chemistry; Protein Conformation; Protein Engineering - methods; Proteins; Proteins - chemical synthesis; Simulations; Water; Wave diffraction; Waxes; X ray diffraction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0700801104

We have established a designed system comprising two peptides that coassemble to form long, thickened protein fibers in water. This system can be rationally engineered to alter fiber assembly, stability, and morphology. Here, we show that rational mutations to our original peptide designs lead to structures with a remarkable level of order on the nanoscale that mimics certain natural fibrous assemblies. In the engineered system, the peptides assemble into two-stranded α-helical coiled-coil rods, which pack in axial register in a 3D hexagonal lattice of size 1.824 nm, and with a periodicity of 4.2 nm along the fiber axis. This model is supported by both electron microscopy and x-ray diffraction. Specifically, the fibers display surface striations separated by nanoscale distances that precisely match the 4.2-nm length expected for peptides configured as α-helices as designed. These patterns extend unbroken across the widths (>=50 nm) and lengths (>10 μm) of the fibers. Furthermore, the spacing of the striations can be altered predictably by changing the length of the peptides. These features reflect a high level of internal order within the fibers introduced by the peptide-design process. To our knowledge, this exceptional order, and its persistence along and across the fibers, is unique in a biomimetic system. This work represents a step toward rational bottom-up assembly of nanostructured fibrous biomaterials for potential applications in synthetic biology and nanobiotechnology.