Electrophysiological Characterization of Mechanosensitive Ion Channels in Native Bacterial Membranes

Mechanosensitive (MS) channels detect and respond to changes in the pressure profile of cellular membranes and transduce the mechanical energy into electrical and/or chemical signals. By re-engineering, however, the activation of some MS channels can be triggered by chemical signals such as pH change. Here, for the first time, we have elucidated, at an atomic level, the activation mechanism of an engineered MscL channel in response to the pH changes of the environment through a combination of equilibrium and non-equilibrium molecular dynamics (MD) simulations. The key highlights of our proposed activation mechanism are that: (1) periplasmic loops play a key role in activation, (2) loss of various hydrogen bonding and salt bridge interactions in the engineered MscL channel causes the opening of the channel, and (3) the most significant interactions lost during the activation process are those between the transmembrane (TM) helices 1 and 2 (TM1 and TM2). The orientation-based method in this work for generating and optimizing an open model of engineered MscL is a promising method for generating unknown states of proteins and for studying the activation processes in ion channels. This work facilitates the studies aimed at designing pH-triggered drug delivery liposomes (DDL), which embed MscL as a nanovalve.

show abstract

Electrophysiological Characterization of Mechanosensitive Ion Channels in Native Bacterial Membranes

Cited by 2 publications

References 0 publications

Elucidating the molecular basis of spontaneous activation in an engineered mechanosensitive channel

Elucidating the molecular basis of spontaneous activation in an engineered mechanosensitive channel

Elucidating the Molecular Basis of pH Activation of an Engineered Mechanosensitive Channel

Contact Info

Product

Resources

About