Metal Exchange in the Interprotein Zn^II -Binding Site of the Rad50 Hook Domain: Structural Insights into Cd^II -Induced DNA-Repair Inhibition.

ABSTRACT: Cd^II is a major genotoxic agent that readily displaces Zn^II in a multitude of zinc proteins, abrogates redox homeostasis, and deregulates cellular metalloproteome. To date, this displacement has been described mostly for cysteine(Cys)-rich intraprotein binding sites in certain zinc finger domains and metallothioneins. To visualize how a Zn^II -to-Cd^II swap can affect the target protein's status and thus understand the molecular basis of Cd^II -induced genotoxicity an intermolecular Zn^II -binding site from the crucial DNA repair protein Rad50 and its zinc hook domain were examined. By using a length-varied peptide base, Zn^II -to-Cd^II displacement in Rad50's hook domain is demonstrated to alter it in a bimo

SUBMITTER: Padjasek M 

PROVIDER: S-EPMC7155053 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature