The MerR heavy metal receptor mediates positive activation in a topologically novel transcription complex.
Several physical and chemical signals from the extracellular environment are known to be transduced into changes in gene expression through multiple step pathways; however, mechanisms for triggering cellular responses to heavy metal stress have yet to be elucidated. We demonstrate here one such mechanism that employs a single heavy metal receptor protein, MerR, to directly activate transcription of the bacterial mercuric ion resistance operon. The mercuric ion-MerR complex and E. coli RNA polymerase holoenzyme synergistically bind to the metal responsive promoter in an unprecedented spatial relationship to form transcriptionally competent complexes. The activator binds adjacent to and overlaps with the polymerase molecule between the consensus -35 and -10 promoter regions. Our results support a model for transcriptional activation that includes both effector-induced protein-protein interactions and activator-induced alteration in DNA structure.
O'Halloran
T V
TV
Department of Chemistry, Northwestern University, Evanston, Illinois 60208.
Frantz
B
B
Shin
M K
MK
Ralston
D M
DM
Wright
J G
JG
D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000502:physiology; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases / Q000502:physiology; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008628:Mercury / Q000378:metabolism*; D008969:Molecular Sequence Data; D009875:Operator Regions, Genetic; D011196:Potassium Permanganate / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D011196:Potassium Permanganate; D012321:DNA-Directed RNA Polymerases; D008628:Mercury