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GhoT of the GhoT/GhoS toxin/antitoxin system damages lipid membranes by forming transient pores

Kim, Jun-Seob, Schantz, Allen B., Song, Sooyeon, Kumar, Manish, Wood, Thomas K.
Biochemical and biophysical research communications 2018 v.497 no.2 pp. 467-472
Escherichia coli, adenosine triphosphate, antitoxins, bacterial toxins, bile, circular dichroism spectroscopy, lipid bilayers, lipids, membrane permeability, metabolism, molecular dynamics, prediction, protein structure, proton-motive force, simulation models
GhoT is a bacterial toxin of the type V toxin/antitoxin system that allows Escherichia coli to reduce its metabolism in response to oxidative and bile stress. GhoT functions by increasing membrane permeability and reducing both ATP levels and the proton motive force. However, how GhoT damages the inner membrane has not been elucidated. Here we investigated how GhoT damages membranes by studying its interaction with lipid bilayers and determined that GhoT does not cause macroscopic disruption of the lipid bilayer to increase membrane permeability to the dye carboxyfluorescein. Using circular dichroism, we found that GhoT forms an alpha helical structure in lipid bilayers that agrees with the structure predicted by the I-TASSER protein structure prediction program. The structure generated using I-TASSER was used to conduct coarse-grained molecular dynamics simulations, which indicate that GhoT damages the cell membrane, as a multimer, by forming transient transmembrane pores.