Abstract Creation of Tubular a- Helical Assemblies Through Seven-Helix Coiled Coils By Rui Liu Native coiled-coil sequences can form large bundles composed of four or more helices in which the helix packing arrangements define continuous channels throughout the supramolecular structure. If the number of helices within the assembly and the inter-helical packing arrangements could be controlled, then one might be able to tailor the channel dimensions and chemistry to facilitate binding of specific classes of guest molecules. A recently reported example of a coiled-coil channel based on a seven-helix bundle provides a prototype for the design of such channels from simple helical peptides. The investigators expanded the hydrophobic interface between helices, which resulted in a discrete seven-helix bundle that defined a channel with an interior diameter of 7 Å. A single residue shift in helix registry was observed between adjacent helices, which resulted in an overall shift of seven residues upon closure of the bundle structure. The structure of the seven-helix bundle resembles a screw with an axial translation corresponding to seven residues within the helical assembly. By modifying the sequence of the peptide to promote end-to-end association between the ends of the lock washer structure, peptide 7HSAP1a was created which could self-associate into a helical fibril, and peptide 7HSAP1a-Cap was created as a negative control. CD spectropolarimetry was used to confirm the helical structure of the peptides. TEM studies indicate the presence of high aspect-ratio fibrils of uniform diameter of 7.4 nm for the 7HSAP1a in MES buffer (pH 6.0). The self-assembly behavior for 7HSAP1a peptide was enhanced in MES buffer (pH 6.0, 100 mM KF), but was weakened in distilled H2O. In the case of capped peptide 7HSAP1a-Cap, self-assembly of fibrils was greatly inhibited after thermal annealing of peptide solutions. Fluorescence spectroscopy confirmed the anticipation that the 7HSAP1a peptidemight form coiled-coil channel which trapped PRODAN.
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About this Master's Thesis
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|Creation of Tubular α− Helical Assemblies Through Seven-Helix Coiled Coils ()||2018-08-28||