4m1p

Publication Abstract from PubMed

The copper-sensing operon repressor (CsoR) is representative of a major Cu(I)-sensing family of bacterial metalloregulatory proteins that has evolved to prevent cytoplasmic copper toxicity. It is unknown how Cu(I) binding to tetrameric CsoRs mediates transcriptional derepression of copper resistance genes. A phylogenetic analysis of 227 DUF156 protein members, including biochemically or structurally characterized CsoR/RcnR repressors, reveals that Geobacillus thermodenitrificans (Gt) CsoR characterized here is representative of CsoRs from pathogenic bacilli Listeria monocytogenes and Bacillus anthracis. The 2.56 A structure of Cu(I)-bound Gt CsoR reveals that Cu(I) binding induces a kink in the alpha2-helix between two conserved copper-ligating residues and folds an N-terminal tail (residues 12-19) over the Cu(I) binding site. NMR studies of Gt CsoR reveal that this tail is flexible in the apo-state with these dynamics quenched upon Cu(I) binding. Small angle x-ray scattering experiments on an N-terminally truncated Gt CsoR (Delta2-10) reveal that the Cu(I)-bound tetramer is hydrodynamically more compact than is the apo-state. The implications of these findings for the allosteric mechanisms of other CsoR/RcnR repressors are discussed.

Cu(I)-mediated allosteric switching in a copper-sensing operon repressor (CsoR).,Chang FM, Coyne HJ, Cubillas C, Vinuesa P, Fang X, Ma Z, Ma D, Helmann JD, Garcia-de los Santos A, Wang YX, Dann CE 3rd, Giedroc DP J Biol Chem. 2014 Jul 4;289(27):19204-17. doi: 10.1074/jbc.M114.556704. Epub 2014, May 15. PMID:24831014^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.