Controlling Self-Assembly of a Peptide-Based Material via Metal-Ion Induced Registry Shift

Peptide <b>TZ1C2</b> can populate two distinct orientations: a staggered (out-of-register) fibril and an aligned (in-register) coiled-coil trimer. The coordination of two cadmium ions induces a registry shift that results in a reversible transition between these structural forms. This process recapitulates the self-assembly mechanism of native protein fibrils in which a ligand binding event gates a reversible conformational transition between alternate forms of a folded peptide structure

Structurally Defined Nanoscale Sheets from Self-Assembly of Collagen-Mimetic Peptides

We report the design of two collagen-mimetic peptide sequences, <b>NSI</b> and <b>NSII</b>, that self-assemble into structurally defined nanoscale sheets. The underlying structure of these nanosheets can be understood in terms of the layered packing of collagen triple helices in two dimensions. These nanosheet assemblies represent a novel morphology for collagen-based materials, which, on the basis of their defined structure, may be envisioned as potentially biocompatible platforms for controlled presentation of chemical functionality at the nanoscale. The molecularly programmed self-assembly of peptides <b>NSI</b> and <b>NSII</b> into nanosheets suggests that sequence-specific macromolecules offer significant promise as design elements for two-dimensional (2D) assemblies. This investigation provides a design rubric for fabrication of structurally defined, peptide-based nanosheets using the principles of solution-based self-assembly facilitated through complementary electrostatic interactions

Rational Design of Helical Nanotubes from Self-Assembly of Coiled-Coil Lock Washers

Design of a structurally defined helical assembly is described that involves recoding of the amino acid sequence of peptide <b>GCN4-pAA</b>. In solution and the crystalline state, <b>GCN4-pAA</b> adopts a 7-helix bundle structure that resembles a supramolecular lock washer. Structurally informed mutagenesis of the sequence of <b>GCN4-pAA</b> afforded peptide <b>7HSAP1</b>, which undergoes self-association into a nanotube via noncovalent interactions between complementary interfaces of the coiled-coil lock-washer structures. Biophysical measurements conducted in solution and the solid state over multiple length scales of structural hierarchy are consistent with self-assembly of nanotube structures derived from 7-helix bundle subunits. The dimensions of the supramolecular assemblies are similar to those observed in the crystal structure of <b>GCN4-pAA</b>. Fluorescence studies of the interaction of <b>7HSAP1</b> with the solvatochromic fluorophore PRODAN indicated that the nanotubes could encapsulate shape-appropriate small molecules with high binding affinity

Rational Design of Helical Nanotubes from Self-Assembly of Coiled-Coil Lock Washers

Design of a structurally defined helical assembly is described that involves recoding of the amino acid sequence of peptide <b>GCN4-pAA</b>. In solution and the crystalline state, <b>GCN4-pAA</b> adopts a 7-helix bundle structure that resembles a supramolecular lock washer. Structurally informed mutagenesis of the sequence of <b>GCN4-pAA</b> afforded peptide <b>7HSAP1</b>, which undergoes self-association into a nanotube via noncovalent interactions between complementary interfaces of the coiled-coil lock-washer structures. Biophysical measurements conducted in solution and the solid state over multiple length scales of structural hierarchy are consistent with self-assembly of nanotube structures derived from 7-helix bundle subunits. The dimensions of the supramolecular assemblies are similar to those observed in the crystal structure of <b>GCN4-pAA</b>. Fluorescence studies of the interaction of <b>7HSAP1</b> with the solvatochromic fluorophore PRODAN indicated that the nanotubes could encapsulate shape-appropriate small molecules with high binding affinity