The copper-responsive repressor CopR of Lactococcus lactis is a ‘winged helix’ protein

Abstract

CopR of Lactococcus lactis is a copper-responsive repressor involved in copper homoeostasis. It controls the expression of a total of 11 genes, the CopR regulon, in a copper-dependent manner. In the absence of copper, CopR binds to the promoters of the CopR regulon. Copper releases CopR from the promoters, allowing transcription of the downstream genes to proceed. CopR binds through its N-terminal domain to a 'cop box' of consensus TACANNTGTA, which is conserved in Firmicutes. We have solved the NMR solution structure of the N-terminal DNA-binding domain of CopR. The protein fold has a winged helix structure resembling that of the BlaI repressor which regulates antibiotic resistance in Bacillus licheniformis. CopR differs from other copper-responsive repressors, and the present structure represents a novel family of copper regulators, which we propose to call the CopY family.

Responses of Lactic Acid Bacteria to Heavy Metal Stress

“…9.4a) (Garcia-Castellanos et al 2004;Himeno et al 1986;Van Melckebeke et al 2003;Wittman and Wong 1988). The structure of the N-terminus of CopR of L. lactis, a CopY-homolog, has been solved by solution NMR (Cantini et al 2009) and is in fact nearly superimposable on the structure of BlaI of Bacillus licheniformis (Fig. 9.4b).…”

Bacterial Copper Resistance and Virulence

“…In contrast to the activators, the interaction of Cu(I) to the regulator provokes their dissociation from the DNA, leading to the induction of transcription as the result of the derepression. CsoY from E. hirae was the first member of the family to be identified [62], and afterwards, other homologues were detected in Gram positive species [61,[63][64][65]. The active repressor form of CopY is an homodimer with zinc bound.…”

Cellular copper distribution: a mechanistic systems biology approach

“…Many transcription factors bind to DNA repeats as dimers to regulate transcription of the target genes. Previous evidences of copper-responsive transcription regulators that bind to DNA repeats existed in bacteria [90], some of which are forming copper-dependent homodimers. X-ray crystallography and biochemical analyses indicated the possibility of a copper-dependent Hah1 homodimerization both in vivo and in vitro [87,91], which would initiate transcription in the nucleus.…”