Structural Studies by LBNL Researcher Provides Insights into Regulation of Bacterial Gene Expression


Many microbes use two-component signal transduction as a method of information processing to control their adaptive behaviors in response to changes in the environment. The transmitter component receives the initial signal and modifies the receiver domain of the second component, called a response regulator; the signal pathway is then turned on or off by the status of the response regulator. Microbial nitrogen assimilation and metabolism is regulated by this type of two-component signal relay, with the NtrC response regulator controlling nitrogen scavenging pathways and nitrogen fixation. Featured on the cover of the June 1, 2006, issue of Genes and Development, LBNL investigator Professor Eva Nogales and colleagues report x-ray and electron microscopy structural biology studies of NtrC that provide new insights into the mechanism of regulation of bacterial transcription and gene expression. When activated by phosphorylation of its receiver domain, NtrC assembles into a donut-like hexameric ring that encloses and binds to regulatory promoter DNA sequences. The resulting conformational change in the molecular machine that produces mRNA, s54-RNA polymerase, thereby activates the entire polymerase machinery to initiate transcription of the required nitrogen assimilation genes, to produce a metabolic response to the original signal about the cells nutrient status. This new model suggests that conformational dynamics are crucial for understanding how a transcriptional activator interacts with RNA polymerase to regulate gene expression.


Sacha De Carlo, Baoyu Chen, Timothy R. Hoover, Elena Kondrashkina, Eva Nogales, and B. Tracy Nixon (2006) The Structural Basis for Regulated Assembly and Function of the Transcriptional Activator NtrC, Genes & Dev 20 (11):1485 1495.