Switchable Zinc(II)-Responsive Globular β-Sheet Peptide

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2022
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Pham, Truc Lam
Thomas, Franziska
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The natural function of many proteins depends on their ability to switch their conformation driven by environmental changes. In this work, we present a small, monomeric β-sheet peptide that switches between a molten globule and a folded state through Zn(II) binding. The solvent-exposed hydrophobic core on the β-sheet surface was substituted by a His3-site, whereas the internal hydrophobic core was left intact. Zn(II) is specifically recognized by the peptide relative to other divalent metal ions, binds in the lower micromolar range, and can be removed and re-added without denaturation of the peptide. In addition, the peptide is fully pH-switchable, has a pKa of about 6, and survives several cycles of acidification and neutralization. In-depth structural characterization of the switch was achieved by concerted application of circular dichroism (CD) and multinuclear NMR spectroscopy. Thus, this study represents a viable approach toward a globular β-sheet Zn(II) mini-receptor prototype.

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ISO 690PHAM, Truc Lam, Michael KOVERMANN, Franziska THOMAS, 2022. Switchable Zinc(II)-Responsive Globular β-Sheet Peptide. In: ACS Synthetic Biology. American Chemical Society (ACS). 2022, 11(1), pp. 254-264. eISSN 2161-5063. Available under: doi: 10.1021/acssynbio.1c00396
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@article{Pham2022Switc-56421,
  year={2022},
  doi={10.1021/acssynbio.1c00396},
  title={Switchable Zinc(II)-Responsive Globular β-Sheet Peptide},
  number={1},
  volume={11},
  journal={ACS Synthetic Biology},
  pages={254--264},
  author={Pham, Truc Lam and Kovermann, Michael and Thomas, Franziska}
}
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