Tying Up a Loose End: On the Role of the C‐Terminal CCHHRAG Fragment of the Metalloregulator CueR. (5th July 2022)

• Record Type: Journal Article
• Authors: Balogh, Ria K.; Gyurcsik, Béla; Jensen, Mikael; Thulstrup, Peter W.; Köster, Ulli; Christensen, Niels Johan; Jensen, Marianne L.; Hunyadi‐Gulyás, Éva; Hemmingsen, Lars; Jancsó, Attila
• Is Part Of: Chembiochem. Volume 23:Number 16(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-05
• Subjects: metalloproteins -- metalloregulatory proteins -- protein metal site structures -- silver -- thiolate coordination; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200290
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: The transcriptional regulator CueR is activated by the binding of Cu I, Ag I, or Au I to two cysteinates in a near‐linear fashion. The C‐terminal CCHHRAG sequence in Escherichia coli CueR present potential additional metal binding ligands and here we explore the effect of deleting this fragment on the binding of Ag I to CueR. CD spectroscopic and ESI‐MS data indicate that the high Ag I ‐binding affinity of WT‐CueR is significantly reduced in Δ7C‐CueR. [111 Ag PAC spectroscopy demonstrates that the WT‐CueR metal site structure (AgS2 ) is conserved, but less populated in the truncated variant. Thus, the function of the C‐terminal fragment may be to stabilize the two‐coordinate metal site for cognate monovalent metal ions. In a broader perspective this is an example of residues beyond the second coordination sphere affecting metal site physicochemical properties while leaving the structure unperturbed. Abstract : The C‐terminal "tail" of CueR does not influence the overall structure of the protein and the structure of the functional metal site but significantly affects the binding affinity for monovalent metal ions, despite being disordered and relatively remote, i. e. beyond the second coordination sphere of Ag I coordinated at the functional metal binding loop.