MMS discovers ligand binding interaction in situ: The bile sensing system of Vibrio cholerae’s ToxRSp protein complex

Studying structure-function relationships of proteins is not only key for the fundamental understanding of cellular processes, but also holds immense potential for applications in drug development. Structural changes in proteins can be triggered by ligand binding interactions, often involving changes in their three-dimensional configuration, ranging from local perturbations to global conformational changes.

Microfluidic Modulation Spectroscopy (MMS) has been shown to serve as a sensitive reporter for the smallest changes in protein secondary structure which provides profound insights into the overall protein arrangement. In this work, we employ MMS to study the impact of ligand binding interaction between bile acid and ToxRSp, the periplasmic domains of ToxRS, which is a sensory protein complex known to trigger virulence and stress responses in Vibrio species. Here, we studied ToxRSp of Vibrio cholerae, the causative of cholera disease. The goal of this application note is to compare the proposed, Molecular Dynamics (MD)- based, binding interaction with experimental findings and to relate the structural changes to implications for the sensory mechanism of the protein complex. For that, we study the structural changes of the complex in the presence of different concentrations of bile acid.

This work was part of a larger, peer-reviewed publication that can be accessed at: Vibrio cholerae's ToxRS bile sensing system | eLife(elifesciences.org)

Want to hear more about this work? Watch our informative webinar featuring Dr. Nina Gubensak, author of the peer-reviewed publication.