Metal-directed self-assembly in a beta-sheet miniprotein scaffold
Natural proteins exploit oligomerization, buried hydrophobic pockets, and metal coordination to drive catalysis and signaling. Miniproteins, as simplified protein-like scaffolds, provide a tractable system for studying sequence-structure-function relationships while leveraging chemical synthesis to...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 March 2026
|
| In: |
European journal of inorganic chemistry
Year: 2026, Volume: 29, Issue: 7, Pages: 1-9 |
| ISSN: | 1099-0682 |
| DOI: | 10.1002/ejic.202500444 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ejic.202500444 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ejic.202500444 
|
| Author Notes: | Chandan Muni Reddy, Marcos R. Conde González, Jürgen H. Gross, Franziska Thomas |
| Summary: | Natural proteins exploit oligomerization, buried hydrophobic pockets, and metal coordination to drive catalysis and signaling. Miniproteins, as simplified protein-like scaffolds, provide a tractable system for studying sequence-structure-function relationships while leveraging chemical synthesis to explore chemical space beyond biological constraints. Here, we introduce V14C, a miniprotein scaffold derived from the 27-residue “Foldon” domain of T4-fibritin, which oligomerizes into a trimer by selectively binding to zinc and cadmium within its hydrophobic pocket. Circular dichroism (CD) spectroscopy, fluorescence spectroscopy, and electrospray ionization-mass spectrometry (ESI-MS), demonstrate that V14C binds to Zn2+ with a dissociation constant of 8.5 µM. Since V14C is a weakly trimerizing Foldon variant, strong thiophilic heavy metal ions like Hg2+ and Cd2+ can impose their preferred coordination geometry on its scaffold. Consequently, V14C-Hg2+ forms a dimer, while V14C-Cd2+ assembles into a native-like trimer. This work demonstrates the potential of identifying and rationally engineering stably folding natural domains to obtain miniprotein scaffolds with new properties. Such top-down engineered systems can be used to explore new chemical environments, expand the toolkit for metallo-protein studies and promote the rational design of functional biomolecular architectures for potential applications in sensing and catalysis. |
|---|---|
| Item Description: | Zuerst veröffentlicht: 05. Januar 2026 Gesehen am 09.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1099-0682 |
| DOI: | 10.1002/ejic.202500444 |