Two component regulation
Our laboratory is interested in OmpR-dependent mechanisms of gene
regulation in a variety of microorganisms. Our work is focused in three areas,
with OmpR
at the center. The signal transduction system that we have devoted our
early efforts to studying is the regulation of outer membrane proteins (Omps) by
EnvZ/OmpR. We are presently applying the experience gained from studying OmpR to
understanding the role OmpR plays in Salmonella pathogenesis. In Salmonella, OmpR
activates genes that are outside of its normal repertoire (ssrA/B in S. typhimurium).
Our goals are to understand the signals that stimulate OmpR to function at these
loci and to understand their regulation. We are interested in understanding the
role of OmpR as a global regulator. In prokaryotes and eukaryotes, a number of
environmental sensing systems are now classified as two-component regulatory systems.
The first component is a protein that serves as a sensor that receives and transduces
the information from the external environment. The second component is a regulator protein.
The EnvZ/OmpR system for porin gene regulation belongs to this group.
Two-component systems are intimately involved in the coordinate expression
of virulence factors in many different pathogens. These systems utilize the
transfer of a phosphoryl group from intracellular ATP to the sensor and onto the
regulator, which then modifies its specific response, usually activation of
transcription. EnvZ
, the 'osmosensor', is an integral protein of the cytoplasmic
membrane composed of 450 amino acid residues arranged in two membrane-spanning
segments, separated by a periplasmic loop and a large cytoplasmic C-terminal
portion. OmpR is a soluble protein of 239 amino acids and functions as a
transcriptional regulator of the ompF and ompC genes
. The signal that is transduced
by EnvZ is unknown, but regulation requires the presence of a periplasmic loop as
well as His 243, the site of phosphorylation in the cytoplasmic domain. We employ
a unique combination of structural, biophysical, biochemical, genetic and molecular
approaches in order to understand these signaling systems at the molecular level.
Publications
Publications may be accessed here: ncbi (will open in a new window or tab)