Two-component signal transduction systems are a common prokaryotic means for sensing environmental stimulus and providing appropriate cellular response. In NtrC system,s the first component (a histidine kinase) senses an environmental change and auto-phosphorylates. The phosphoryl signal is transferred to the three-domain transcription factor. These transcription factors, also known as response regulators, contain a regulatory domain (which accepts the phosphoryl signal), a central ATPase domain, and a DNA-binding domain. We study the structure and mechanisms of these response regulators from the extreme thermophilic bacteria Aquifex aeolicus using a combination of NMR spectroscopy, X-ray crystallography, Short Angle X-ray Scattering, and other biophysical techniques, in order to better understand the process of bacterial transcription.
NtrC-like proteins, NtrC1 and NtrC4, belong to a special subfamily of response regulators that activate transcription via interaction with sigma 54 of the RNA polymerase holocomplex. Current NtrC-related questions include:
How is the activation signal transmitted intramolecularly?
How are the DNA promoter sites recognized? How is this recognition different in thermophilic bacteria?
How do NtrC-like proteins signal sigma-54?
How do homologues and paralogues differ functionally and structurally?
We also study the structure and function of the sigma54 factor, including the structure of its individual domains, the structural requirements for function, and the DNA-binding activity.
Understanding these mechanisms provides basic knowledge in protein-protein and protein-DNA biochemistry, as well as contributes information which can be applied to virulent homologues in other two-component systems.
