MagicWand: A single designed peptide that assembles to stable, ordered α-helical fibers

C Gribbon, KJ Channon, W Zhang, EF Banwell, EHC Bromley, JB Chaudhuri, ROC Oreffo, DN Woolfson

Research output: Contribution to journalArticle (Academic Journal)

Abstract

We describe a straightforward single-peptide design that self-assembles into extended and thickened nano-to-mesoscale fibers of remarkable stability and order. The basic chassis of the design is the well-understood dimeric α-helical coiled-coil motif. As such, the peptide has a heptad sequence repeat, abcdefg, with isoleucine and leucine residues at the a and d sites to ensure dimerization. In addition, to direct staggered assembly of peptides and to foster fibrillogenesisthat is, as opposed to blunt-ended discrete speciesthe terminal quarters of the peptide are cationic and the central half anionic with lysine and glutamate, respectively, at core-flanking e and g positions. This +,−,−,+ arrangement gives the peptide its name, MagicWand (MW). As judged by circular dichroism (CD) spectra, MW assembles to α-helical structures in the sub-micromolar range and above. The thermal unfolding of MW is reversible with a melting temperature >70 °C at 100 μM peptide concentration. Negative-stain transmission electron microscopy (TEM) of MW assemblies reveals stiff, straight, fibrous rods that extended for tens of microns. Moreover, different stains highlight considerable order both perpendicular and parallel to the fiber long axis. The dimensions of these features are consistent with bundles of long, straight coiled α-helical coiled coils with their axes aligned parallel to the long axis of the fibers. The fiber thickening indicates inter-coiled-coil interactions. Mutagenesis of the outer surface of the peptidei.e., at the b and f positionscombined with stability and microscopy measurements, highlights the role of electrostatic and cation−π interactions in driving fiber formation, stability and thickening. These findings are discussed in the context of the growing number of self-assembling peptide-based fibrous systems.
Translated title of the contributionMagicWand: A single designed peptide that assembles to stable, ordered α-helical fibers
Original languageEnglish
Pages (from-to)10365 - 10371
Number of pages7
JournalBiochemistry
Volume47
Issue number39
DOIs
Publication statusPublished - Sep 2008

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    Gribbon, C., Channon, KJ., Zhang, W., Banwell, EF., Bromley, EHC., Chaudhuri, JB., Oreffo, ROC., & Woolfson, DN. (2008). MagicWand: A single designed peptide that assembles to stable, ordered α-helical fibers. Biochemistry, 47(39), 10365 - 10371. https://doi.org/10.1021/bi801072