Article Source: University of East Anglia
Abstract: Scientists have found molecular details of how different pathogenic bacteria survive the human immune response and cause infection. They have also identified the structure of NsrR, a bacterial protein that binds to DNA and helps in the bacterium’s resistance to nitric oxide (NO), which is produced during the initial immune response to infection.
In a new research carried out by Researchers at the University of East Anglia (UEA) and Institut de Biologie Structurale (CEA-CNRS-UGA), the structure of a bacterial protein NsrR which binds to DNA has been identified. According to researchers, the bacterial protein NsrR plays a significant role in the bacterium’s resistance to nitric oxide (NO), which is produced in the initial immune response to infection.
The research has helped researchers reveal molecular details of how pathogenic bacteria fight back against the human immune response to infection.
The scientists also report that the bacteria have evolved ways to detect and counter the effects of NO, a gas that can be toxic to living organisms.
The most common dedicated NO sensor in bacteria is the regulatory protein NsrR. Regulatory proteins bind to DNA and while doing so, they control whether particular genes are switched on or off.
The NsrR protein is also found to contain a specialised type of co-factor, called an iron-sulfur cluster which is an additional component of a protein required for its activity. This makes NsrR protein very fragile and reactive, which makes it hard to work with, but recent work in the Schools of Chemistry and Biology at UEA have provided important new information on how NsrR functions as a sensor of NO.
The group has now identified structures of the protein in its two principal forms — cluster-free and cluster-bound — revealing crucial differences that show the response of NsrR towards NO.
These structural changes show how NsrR switches between DNA-binding and non-binding forms, enabling it to regulate the switching on or off of the production of enzymes which combat NO.
According to Prof Nick Le Brun, the lead researcher at UEA, said: “NsrR belongs to an important but poorly understood family of regulators, members of which are involved in a wide range of essential cellular functions in bacteria.
“Many of these regulators have been shown or are predicted to contain an iron-sulfur cluster, but our work provides the first example of a structure with the fragile cluster bound. It reveals the general mechanism by which these regulators respond to different signals.
“Furthermore, the structure reveals that the cluster is coordinated to the protein in a way that has not been observed before in biology.
“The process of how pathogens survive human immune responses is complex, and every step we take towards understanding it, the greater the possibility of developing intervention strategies that disable the response.”
The research has been published in a paper titled ‘Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding’ in the journal Nature Communications.
Anne Volbeda, Erin L. Dodd, Claudine Darnault, Jason C. Crack, Oriane Renoux, Matthew I. Hutchings, Nick E. Le Brun, Juan C. Fontecilla-Camps. Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding. Nature Communications, 2017; 8: 15052 DOI: 10.1038/NCOMMS15052