Metalloregulator CueR biases RNA polymerase’s kinetic sampling of dead-end or open complex to repress or activate transcription
Abstract
MerR-family regulators act on suboptimal promoters to control the transcriptions of genes that help bacteria defend against a diverse set of metals and drugs. How they modulate RNA polymerase (RNAP) activity to control transcription initiation remains unclear, however. Here we show that CueR—a Cu + -responsive MerR-family metalloregulator—biases the kinetic sampling of RNAP binding events that lead to two noninterconverting states: a dead-end complex to repress or an open complex to activate transcription, constituting a branched pathway distinct from the linear pathway prevalent for transcription initiation at optimal promoters. This mechanistic insight contributes new fundamental knowledge to bacterial transcription regulation, and may help develop antibiotics that target this regulation mechanism to compromise bacterial defenses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 19, 2015
- Source ID
- 10.1073/pnas.1515231112
Entities
People
- Ace George Santiago
- Ahmed Gaballa
- Chandra P. Joshi
- Danya J. Martell
- John D. Helmann
- Peng Chen
- Tai-Yen Chen
- Won Jung
Organizations
- Army Research Office
- Cornell University
- National Institute of Allergy and Infectious Diseases
- National Institute of General Medical Sciences