Premium
C‐terminal Cysteines of CueR Act as Auxiliary Metal Site Ligands upon Hg II Binding—A Mechanism To Prevent Transcriptional Activation by Divalent Metal Ions?
Author(s) -
Balogh Ria K.,
Gyurcsik Béla,
HunyadiGulyás Éva,
Schell Juliana,
Thulstrup Peter W.,
Hemmingsen Lars,
Jancsó Attila
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902940
Subject(s) - chemistry , binding site , metal , divalent , transcription (linguistics) , stereochemistry , metal ions in aqueous solution , biophysics , crystallography , biochemistry , biology , philosophy , linguistics , organic chemistry
Intracellular Cu I is controlled by the transcriptional regulator CueR, which effectively discriminates between monovalent and divalent metal ions. It is intriguing that Hg II does not activate transcription, as bis‐thiolate metal sites exhibit high affinity for Hg II . Here the binding of Hg II to CueR and a truncated variant, ΔC7‐CueR, without the last 7 amino acids at the C‐terminus including a conserved CCHH motif is explored. ESI‐MS demonstrates that up to two Hg II bind to CueR, while ΔC7‐CueR accommodates only one Hg II . 199m Hg PAC and UV absorption spectroscopy indicate HgS 2 structure at both the functional and the CCHH metal site. However, at sub‐equimolar concentrations of Hg II at pH 8.0, the metal binding site displays an equilibrium between HgS 2 and HgS 3 , involving cysteines from both sites. We hypothesize that the C‐terminal CCHH motif provides auxiliary ligands that coordinate to Hg II and thereby prevents activation of transcription.