Publication Date:
2014-01-28
Description:
Metal ion homeostasis in bacteria relies on metalloregulatory proteins to upregulate metal resistance genes and enable the organism to preclude metal toxicity. The copper sensitive operon repressor (CsoR) family is widely distributed in bacteria and controls the expression of copper efflux systems. CsoR operator sites consist of G-tract containing pseudopalindromes of which the mechanism of operator binding is poorly understood. Here, we use a structurally characterized CsoR from Streptomyces lividans (CsoR Sl ) together with three specific operator targets to reveal the salient features pertaining to the mechanism of DNA binding. We reveal that CsoR Sl binds to its operator site through a 2-fold axis of symmetry centred on a conserved 5'-TAC/GTA-3' inverted repeat. Operator recognition is stringently dependent not only on electropositive residues but also on a conserved polar glutamine residue. Thermodynamic and circular dichroic signatures of the CsoR Sl –DNA interaction suggest selectivity towards the A-DNA-like topology of the G-tracts at the operator site. Such properties are enhanced on protein binding thus enabling the symmetrical binding of two CsoR Sl tetramers. Finally, differential binding modes may exist in operator sites having more than one 5'-TAC/GTA-3' inverted repeat with implications in vivo for a mechanism of modular control.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
