Omega Currents in Voltage-Gated Ion Channels: What Can We Learn from Uncovering the Voltage-Sensing Mechanism Using MD Simulations?

2013 ◽  
Vol 46 (12) ◽  
pp. 2755-2762 ◽  
Author(s):  
Mounir Tarek ◽  
Lucie Delemotte
2018 ◽  
Author(s):  
Marina A. Kasimova ◽  
Erik Lindahl ◽  
Lucie Delemotte

ABSTRACTVoltage-sensitive membrane proteins are united by the ability to transform changes in the membrane potential into mechanical work. They are responsible for a spectrum of key physiological processes in living organisms, including electric signaling and progression along the cell cycle. While the voltage-sensing mechanism has been well characterized for some membrane proteins such as voltage-gated ion channels, for others even the location of the voltage-sensing elements remains unknown. The detection of these elements using experimental techniques is complicated due to the large diversity of membrane proteins. Here, we suggest a computational approach to predict voltage-sensing elements in any membrane protein independent of structure or function. It relies on the estimation of the capacity of a protein to respond to changes in the membrane potential. We first show how this property correlates well with voltage sensitivity by applying our approach to a set of membrane proteins including voltage-sensitive and voltage-insensitive ones. We further show that it correctly identifies true voltage-sensitive residues in the voltage sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions potentially involved in the response to voltage. The suggested approach is fast and simple and allows for characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application prior to mutagenesis experiments will allow for significant reduction of the number of potential voltage-sensitive elements to be tested.


2018 ◽  
Vol 150 (10) ◽  
pp. 1444-1458 ◽  
Author(s):  
Marina A. Kasimova ◽  
Erik Lindahl ◽  
Lucie Delemotte

Voltage-sensitive membrane proteins are united by their ability to transform changes in membrane potential into mechanical work. They are responsible for a spectrum of physiological processes in living organisms, including electrical signaling and cell-cycle progression. Although the mechanism of voltage-sensing has been well characterized for some membrane proteins, including voltage-gated ion channels, even the location of the voltage-sensing elements remains unknown for others. Moreover, the detection of these elements by using experimental techniques is challenging because of the diversity of membrane proteins. Here, we provide a computational approach to predict voltage-sensing elements in any membrane protein, independent of its structure or function. It relies on an estimation of the propensity of a protein to respond to changes in membrane potential. We first show that this property correlates well with voltage sensitivity by applying our approach to a set of voltage-sensitive and voltage-insensitive membrane proteins. We further show that it correctly identifies authentic voltage-sensitive residues in the voltage-sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions that might be involved in the response to voltage. The suggested approach is fast and simple and enables a characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application before mutagenesis experiments will significantly reduce the number of potential voltage-sensitive elements to be tested.


2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  

2009 ◽  
Vol 96 (3) ◽  
pp. 261a
Author(s):  
Muugu V. Brahmajothi ◽  
Michael. J. Morales ◽  
Donald L. Campbell ◽  
Charles Steenbergen ◽  
Harold C. Strauss

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