The molecular mechanism of transmembrane signaling in bacterial chemotaxis system as mediated by membrane proteins

Bacterial chemotaxis is an ideal system to investigate the underlying mechanism involved in transmembrane signaling, by membrane proteins.  Bacteria are able to sense chemicals from their environment and direct their swimming toward more favorable environments.  Repellant or attractant molecules bind to the periplasmic region of the transmembrane receptor, and the signal is transmitted through the receptor across the membrane to the cytoplasmic region, which modulates the motility of the cell.  This response is mediated by an array of receptors along with two other proteins, CheA and CheW, at the poles of the cell. Previous studies have shown that the cytoplasmic domain of the receptor is highly dynamic in nature, and it has been proposed that changes in the dynamics play an important role in the signaling mechanism.  My project focuses in understanding the role played by dynamics of chemoreceptors in transmembrane signaling. We developed a novel method to monitor changes in dynamics of cytoplasmic domain in functional signaling complexes using hydrogen exchange mass spectrometry. Our data show that the global dynamics of cytoplasmic domain are significantly reduced in active complexes.  Currently we are optimizing conditions that would allow us to measure local dynamics of cytoplasmic domain in a functional complex, this would enable us to determine the role played by dynamics of different regions of cytoplasmic domain in transmembrane signaling.