Computational Studies of Membrane Fluidity Sensor DesK
Abstract
Molecular Dynamics simulations (MD) were used to study how lipids interact with proteins, how proteins interact with each other in biological membranes, and the effects that the lipid environment has on these interactions. These studies were performed on the bacterial sensor protein DesK, which acts as a molecular switch to maintain membrane fluidity under different temperature conditions. Studies of pure lipid bilayers were performed to establish the effect of temperature on the pure bilayer as reflected by MD simulation. Interaction studies of proteins and lipids were performed on a minimal sensor protein, MS-DesK, identified experimentally as well as multiple representative Transmembrane Domain (TMD) peptides. The response of single instances of peptide (monomers) to change in temperature and bilayer thickness were studied with a focus on peptide location and orientation with respect to the bilayer, providing support for a thickness-based sensing mechanism. Further, the response of pairs of peptides (dimers) to change in membrane thickness and temperature was examined. Specifically, the role of helix-helix interactions in the mechanism of function of the protein was used to compare with different published models of function with a focus on the roles of sensing and signaling motifs. Following both experimental and theoretical observations the sequence of the linker peptide was examined for its role in signaling activity and protein function. This study shows that the protein is strongly located in the bilayer and that a thickness based sensing mechanism is viable. It also shows that previous suggestions of peptides sticking out of the bilayer are not supported by modeling results. The computations suggest that anchoring of both ends of the TMD to the boundaries of the bilayer and the change of the bilayer are most strongly correlated with protein activity.
Description
Keywords
Biochemistry
Citation
Moussatova, A. (2015). Computational Studies of Membrane Fluidity Sensor DesK (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25398