Structural Insight Into a Human H Ferritin@Gold‐Monocarbene Adduct: Aurophilicity Revealed in a Biological Context
Abstract
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.
Article Details
Authors (10)
Lucrezia Cosottini
Department of Chemistry “Ugo Schiff” University of Florence Via della Lastruccia 3–13 Sesto Fiorentino 50019 Italy
Andrea Giachetti
Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP) Sesto Fiorentino FI 50019 Italy
Annalisa Guerri
Department of Chemistry “Ugo Schiff” University of Florence Via della Lastruccia 3–13 Sesto Fiorentino 50019 Italy
Ane Martinez‐Castillo
Structure and Cell Biology of Viruses Lab Center for Cooperative Research in Biosciences (CIC bioGUNE) Basque Research and Technology Alliance (BRTA) Derio Spain
Andrea Geri
Department of Chemistry “Ugo Schiff” University of Florence Via della Lastruccia 3–13 Sesto Fiorentino 50019 Italy
Stefano Zineddu
Department of Chemistry “Ugo Schiff” University of Florence Via della Lastruccia 3–13 Sesto Fiorentino 50019 Italy
Nicola G. A. Abrescia
Structure and Cell Biology of Viruses Lab Center for Cooperative Research in Biosciences (CIC bioGUNE) Basque Research and Technology Alliance (BRTA) Derio Spain
Luigi Messori
Department of Chemistry “Ugo Schiff” University of Florence Via della Lastruccia 3–13 Sesto Fiorentino 50019 Italy
Paola Turano
Antonio Rosato