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Updated: May 11, 2025
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Synthesis and Catalytic Performance of Gold Intercalated in the Walls of Mesoporous Silica
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Structural Insight Into a Human H Ferritin@Gold-Monocarbene Adduct: Aurophilicity Revealed in a Biological Context
Lucrezia Cosottini1, Andrea Giachetti2, Annalisa Guerri1
1Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, Sesto Fiorentino, 50019, Italy.
Angewandte Chemie (International Ed. in English)
|April 18, 2025
Summary
Human H ferritin (HuHf) shows potential as a nanocarrier for anticancer drugs. Electrospray ionization-mass spectrometry and cryo-EM revealed gold binding to protein cysteines, forming novel gold clusters.
Area of Science:
- Biochemistry and Structural Biology
- Nanotechnology and Drug Delivery
- Materials Science and Inorganic Chemistry
Background:
- Human H ferritin (HuHf) is a promising nanocarrier for targeted delivery of metal-based anticancer drugs to tumor cells.
- Understanding the interaction between metal-based drugs and protein nanocarriers is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the interaction between the gold monocarbene compound Au(NHC)Cl and Human H ferritin (HuHf).
- To elucidate the binding sites and structural consequences of Au(NHC)Cl complexation with HuHf.
- To demonstrate the utility of cryo-electron microscopy (cryo-EM) for studying metal-protein interactions.
Main Methods:
- Electrospray ionization-mass spectrometry (ESI-MS) was employed to determine the metalation state of HuHf subunits and identify cysteine involvement in gold binding.
- Cryo-electron microscopy (cryo-EM) was used to determine the high-resolution 3D structure of the Au(NHC)Cl-HuHf adduct.
- Analysis of the cryo-EM structure to identify the arrangement and interactions of gold ions within the protein nanocarrier.
Main Results:
- ESI-MS confirmed the binding of gold to HuHf and indicated the involvement of protein cysteines.
- Cryo-EM provided a 1.51 Å resolution 3D map of the Au(NHC)Cl-HuHf complex.
- A novel tetranuclear gold(I) cluster was identified in a surface pocket of each HuHf subunit, coordinated by Cys90 and Cys102, exhibiting aurophilic interactions.
Conclusions:
- The study successfully characterized the interaction of Au(NHC)Cl with HuHf, revealing specific binding sites and the formation of unique gold clusters.
- Cryo-EM is a powerful technique for visualizing metal-drug interactions with protein nanocarriers, aided by the strong signal of transition metals.
- This work provides insights into the structural basis for using HuHf as a nanocarrier for gold-based anticancer agents.
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