Structures of Silver Fingers and a Pathway to Their Genotoxicity

Katarzyna Kluska (1) , Giulia Veronesi (2) , Aurélien Deniaud (3) , Bálint Hajdu (4) , Béla Gyurcsik (4) , Wojciech Bal (1) , Artur Krężel (1)

1 Department of Chemical Biology, Faculty of Biotechnology
2 COMX - Chimie computationnelle, modélisation et rayons X
3 MET&OR - Métaux et Organes
4 Department of Inorganic and Analytical Chemistry, Faculty of Science and Informatics

Recently, we demonstrated that Ag-I can directly replace Zn-II in zinc fingers (ZFs). The cooperative binding of Ag-I to ZFs leads to a thermodynamically irreversible formation of silver clusters destroying the native ZF structure. Thus, a reported loss of biological function of ZF proteins is a likely consequence of such replacement. Here, we report an X-ray absorption spectroscopy (XAS) study of AgnSn clusters formed in ZFs to probe their structural features. Selective probing of the local environment around Ag-I by XAS showed the predominance of digonal Ag-I coordination to two sulfur donors, coordinated with an average Ag-S distance at 2.41 angstrom. No Ag-N bonds were present. A mixed AgS2/AgS3 geometry was found solely in the CCCH Ag-I-ZF. We also show that cooperative replacement of Zn-II ions with the studied Ag2S2 clusters occurred in a three-ZF transcription factor protein 1MEY#, leading to a dissociation of 1MEY# from the complex with its cognate DNA.

Mots clés: DNA Binding; Silver Clusters; Zinc Fingers; X-ray Absorption Spectroscopy

Domaines: Matériaux; Biochimie, Biologie Moléculaire

Katarzyna Kluska, Giulia Veronesi, Aurélien Deniaud, Bálint Hajdu, Béla Gyurcsik, et al.. Structures of Silver Fingers and a Pathway to Their Genotoxicity. Angewandte Chemie International Edition, 2022, 61 (12), pp.e202116621. ⟨10.1002/anie.202116621⟩. ⟨hal-03573144⟩