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

Abstract

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