Download MendeleyStructural Insight Into a Human H Ferritin@Gold-Monocarbene Adduct: Aurophilicity Revealed in a Biological Context.
Cosottini, L., Giachetti, A., Guerri, A., Martinez-Castillo, A., Geri, A., Zineddu, S., Abrescia, N.G.A., Messori, L., Turano, P., Rosato, A.(2025) Angew Chem Int Ed Engl : e202503778-e202503778
- PubMed: 40249912
- DOI: https://doi.org/10.1002/anie.202503778
- Primary Citation of Related Structures:
9HQ6 - PubMed Abstract:
Human H ferritin (HuHf) has excellent potential as a nanocarrier for the selective delivery of anticancer metal-based drugs to tumor cells. Here, we addressed the interaction of the gold monocarbene compound Au(NHC)Cl with HuHf by electrospray ionization-mass spectrometry (ESI-MS)?measurements, which provide the metalation state of the protein subunits and demonstrate the involvement of protein cysteines in gold binding. The adduct between Au(NHC)Cl and HuHf was studied by cryo-EM measurements, resulting in a high-resolution 3D density map at 1.51??. The cryo-EM structure shows a novel tetranuclear gold(I) cluster, located in a surface pocket of each subunit where it is bound to Cys90 and Cys102. The short inter-metal distances are diagnostic of the occurrence of aurophilic interactions. The present work demonstrates the usefulness of cryo-EM to investigate the interactions between metal-based drugs and their protein targets/carriers, also leveraging the strong signal of transition metal ions.
Organizational Affiliation:
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, Sesto Fiorentino, 50019, Italy.
