9HQ6

Structural insights in the HuHf@gold-monocarbene adduct: aurophilicity revealed in a biological context

Summary for 9HQ6

• Entry DOI: 10.2210/pdb9hq6/pdb
• EMDB information: 52339
• Descriptor: Ferritin heavy chain, 1-butyl-3-methyl-1H-imidazol-3-ium, GOLD ION, ... (4 entities in total)
• Functional Keywords: iron, gold, metal transport, metal storage, anticancer drugs, drug nanocarrier, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 24
• Total formula weight: 529237.08

Authors

Cosottini, L.,Giachetti, A.,Guerri, A.,Martinez-Castillo, A.,Geri, A.,Zineddu, S.,Abrescia, N.G.A.,Messori, L.,Turano, P.,Rosato, A. (deposition date: 2024-12-16, release date: 2025-05-07)

Primary citation

Cosottini, L.,Giachetti, A.,Guerri, A.,Martinez-Castillo, A.,Geri, A.,Zineddu, S.,Abrescia, N.G.A.,Messori, L.,Turano, P.,Rosato, A.
Structural Insight Into a Human H Ferritin@Gold-Monocarbene Adduct: Aurophilicity Revealed in a Biological Context.
Angew.Chem.Int.Ed.Engl., :e202503778-e202503778, 2025

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 Å. 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.

PubMed: 40249912
DOI: 10.1002/anie.202503778

Experimental method

ELECTRON MICROSCOPY (1.51 Å)