Prof. Nick Le Brun, University of East Anglia, UK

Iron-Sulfur Cluster Regulatory Proteins as Biological Switches

The ability to sense and respond to various key environmental cues is important for the survival and adaptability of bacteria, including pathogens. The particular sensitivity of iron-sulfur (Fe-S) clusters has been exploited in nature through the evolution of multiple sensor-regulator proteins that use a sensing reaction at their Fe-S cluster to coordinate the detection of environment signals with (in many cases) a global transcriptional response. The fragility and sensitivity of these Fe-S clusters makes studying such proteins difficult, hampering efforts to determine what signals they sense, how they sense them, and how they transduce the signal to affect transcription. In this seminar, I will describe a number of Fe-S cluster regulators under study in my laboratory, and the approaches we have taken to gain structural and functional insight. In particular, I will describe the application of native mass spectrometry to studies of Fe-S proteins and the chemistry taking place at the cluster.