title: Regulation of the Dha operon of Lactococcus lactis: a deviation from the rule followed by the Tetr family of transcription regulators.
abstract: Dihydroxyacetone (Dha) kinases are a novel family of kinases with signaling and metabolic functions. Here we report the x-ray structures of the transcriptional activator DhaS and the coactivator DhaQ and characterize their function. DhaQ is a paralog of the Dha binding Dha kinase subunit; DhaS belongs to the family of TetR repressors although, unlike all known members of this family, it is a transcriptional activator. DhaQ and DhaS form a stable complex that in the presence of Dha activates transcription of the Lactococcus lactis dha operon. Dha covalently binds to DhaQ through a hemiaminal bond with a histidine and thereby induces a conformational change, which is propagated to the surface via a cantilever-like structure. DhaS binding protects an inverted repeat whose sequence is GGACACATN6ATTTGTCC and renders two GC base pairs of the operator DNA hypersensitive to DNase I cleavage. The proximal half-site of the inverted repeat partially overlaps with the predicted -35 consensus sequence of the dha promoter.
authors.affiliation: Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Christen
authors.forename: Annapurna
authors.initials: A
authors.lastname: Srinivas
authors.forename: Priska
authors.initials: P
authors.lastname: Bähler
authors.forename: Anja
authors.initials: A
authors.lastname: Zeller
authors.forename: David
authors.initials: D
authors.lastname: Pridmore
authors.forename: Christoph
authors.initials: C
authors.lastname: Bieniossek
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Erni
mesh_terms: D000595:Amino Acid Sequence; D003850:Deoxyribonuclease I / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D013294:Lactococcus lactis / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009876:Operon; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; C034811:tetracycline resistance-encoding transposon repressor protein; D006639:Histidine; D017853:Phosphotransferases (Alcohol Group Acceptor); C023132:glycerone kinase; D003850:Deoxyribonuclease I