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

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posted on 16.10.2013, 00:00 by Chunfu Xu, Rui Liu, Anil K. Mehta, Ricardo C. Guerrero-Ferreira, Elizabeth R. Wright, Stanislaw Dunin-Horkawicz, Kyle Morris, Louise C. Serpell, Xiaobing Zuo, Joseph S. Wall, Vincent P. Conticello
Design of a structurally defined helical assembly is described that involves recoding of the amino acid sequence of peptide GCN4-pAA. In solution and the crystalline state, GCN4-pAA adopts a 7-helix bundle structure that resembles a supramolecular lock washer. Structurally informed mutagenesis of the sequence of GCN4-pAA afforded peptide 7HSAP1, 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 GCN4-pAA. Fluorescence studies of the interaction of 7HSAP1 with the solvatochromic fluorophore PRODAN indicated that the nanotubes could encapsulate shape-appropriate small molecules with high binding affinity.