Abstract
Protein complexes perform a diversity of functions in natural biological systems. While computational protein design has enabled the development of symmetric protein complexes with spherical shapes and hollow interiors, the individual subunits often comprise large proteins. Peptides have also been applied to self-assembly, and it is of interest to explore such short sequences as building blocks of large, designed complexes. Coiled-coil peptides are promising subunits as they have a symmetric structure that can undergo further assembly. Here, an α-helical 29-residue peptide that forms a tetrameric coiled coil was computationally designed to assemble into a spherical cage that is approximately 9 nm in diameter and presents an interior cavity. The assembly comprises 48 copies of the designed peptide sequence. The design strategy allowed breaking the side chain conformational symmetry within the peptide dimer that formed the building block (asymmetric unit) of the cage. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques showed that one of the seven designed peptide candidates assembled into individual nanocages of the size and shape. The stability of assembled nanocages was found to be sensitive to the assembly pathway and final solution conditions (pH and ionic strength). The nanocages templated the growth of size-specific Au nanoparticles. The computational design serves to illustrate the possibility of designing target assemblies with pre-determined specific dimensions using short, modular coiled-coil forming peptide sequences.
Highlights
Computational protein design has been used extensively in the design of novel protein-based symmetric structures [16,17,18,19,20], but tunability of the interior cage volume has been limited by two factors: the use of natural proteins as building blocks and the need to arrange the subunits in strictly symmetrical arrangements [21]
Rational and computational approaches have been previously used in the design of highly symmetric protein assemblies, such as homo-oligomeric and hetero-oligomeric icosahedral cages derived from naturally occurring proteins [16,17,18,19,22,23,24]
To design self-assembling peptide nanocages, we targeted an assembly of coiledcoils in a spherical arrangement with octahedral symmetry
Summary
While computational protein design has enabled the development of symmetric protein complexes with spherical shapes and hollow interiors, the individual subunits often comprise large proteins. Peptides have been applied to self-assembly, and it is of interest to explore such short sequences as building blocks of large, designed complexes. The computational design serves to illustrate the possibility of designing target assemblies with pre-determined specific dimensions using short, modular coiled-coil forming peptide sequences. Computational protein design has been used extensively in the design of novel protein-based symmetric structures [16,17,18,19,20], but tunability of the interior cage volume has been limited by two factors: the use of natural proteins as building blocks and the need to arrange the subunits in strictly symmetrical arrangements [21].
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