Publication Abstract from PubMed
Enterococcus faecalis is one of the major causes for hospital-acquired antibiotic-resistant infections. It produces an exotoxin, called cytolysin, which is lethal for a wide range of Gram-positive bacteria and is toxic to higher organisms. Recently, the regulation of the cytolysin operon was connected to autoinduction by a quorum-sensing mechanism involving the CylR1/CylR2 two-component regulatory system. We report here the crystal structure of CylR2 and its properties in solution as determined by heteronuclear NMR spectroscopy. The structure reveals a rigid dimer containing a helix-turn-helix DNA-binding motif as part of a five-helix bundle that is extended by an antiparallel beta-sheet. We show that CylR2 is a DNA-binding protein that binds specifically to a 22 bp fragment of the cytolysin promoter region. NMR chemical shift perturbation experiments identify surfaces involved in DNA binding and are in agreement with a model for the CylR2/DNA complex that attributes binding specificity to a complex network of CylR2/DNA interactions. Our results propose a mechanism where repression is achieved by CylR2 obstruction of the promoter preventing biosynthesis of the cytolysin operon transcript.
Structure and DNA-binding properties of the cytolysin regulator CylR2 from Enterococcus faecalis.,Rumpel S, Razeto A, Pillar CM, Vijayan V, Taylor A, Giller K, Gilmore MS, Becker S, Zweckstetter M EMBO J. 2004 Sep 15;23(18):3632-42. Epub 2004 Sep 9. PMID:15359276[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
