Investigation of the Signal Sensing Mechanism by the Bacterial Thermosensor Desk using Molecular Dynamics Methods

Abstract

DesK is a protein responsible for the regulation of membrane fluidity in Bacilus subtilis. In the present study Molecular Dynamics (MD) simulations are used to explore the details of the molecular mechanism by which DesK is capable of sensing changes in membrane properties in response to variations in temperature. This study was prompted by the development of a DesK minimal sensor (DesK-MS) that captures the two functions of this protein: the sensing of an environmental signal and the transduction of this signal through the membrane to the cytoplasmic side of the cell [1]. Structurally, the DesK-MS has a single transmembrane (TM) helix, in contrast with the five TM helices of the complete DesK protein. Multiple mutants based on the TM part of DesK-MS have been reported, suggesting that DesK is sensitive to changes in membrane thickness as a result of changes in temperature. In our study we have used model peptides representing the TM part of the DesK-MS, both the wild type and some of its mutants. These peptides were embedded into various model bilayers and the MD simulations performed at different temperatures. The behavior of model peptides in response to the changes in thickness of the bilayer due to variations in temperature was observed and characterized by its motion, interfacial positioning and tilt and rotation angles.[1] Cybulski, L.E., et.al., Membrane thickness cue for cold sensing in bacterium, Curr. Biology (2010) 20:7