What causes the opening and closing of our cells’ communication pathways?

Title: Probing the Effects of Gating on the Ion Occupancy of the K+ Channel Selectivity Filter Using Two-Dimensional Infrared Spectroscopy

Authors: Huong T. Kratochvil, Eduardo Perozo, Michal Maj, Benoît Roux, Kimberly Matulef, Francis I. Valiyaveetil, Alvin W. Annen, Jared Ostmeyer, and Martin T. Zanni

Year: 2017

Journal: Journal of the American Chemical Society

This study dives deep into the inner workings of a crucial part of our bodies’ cells, ion channels, which help to send electrical signals through our cells allowing nervous and muscular functions to occur. The researchers find that they are able to use this technique to discern if the gates in the channels are open or closed, the percentage amount that each gate open for communication, and how the communication changes the structure of the ion channels.

In order to do this study, the researchers used a technique called 2D infrared spectroscopy (2DIR). In standard 1D infrared spectroscopy, light is shone at molecules in order to observe the vibrations induced by the energy the light carries. With the added dimension, researchers are able to look for correlations between each individual vibrations, looking at what bonds are vibrating and how they are interacting with other vibrations in the sample.

The system being looked at are proteins in our cells that sit in the cell wall and act as a gateway for potassium ions to leave the cells. This phenomenon is crucial for communication, as the potassium ions act as a channel for electrical signals, with other cells. In these proteins, there are actually two gates, much like how people have the gate in their fence surrounding their home and a door to get inside. The structure of the proteins and their two gates can be seen in figure 1.

Figure 1: A schematic of the protein where the potassium ions are shown in purple. Here both gates are located below the ions and are both shown in their closed conformation.

The researchers found two peaks, corresponding to two different vibrations, in their spectra of the open and closed gates structures. However, more interesting than these peaks themselves, was the shift in the energy that the peaks appeared at between the two structures. This meant that something significant must have changed within the protein structure.

In order to assign what vibrations in the protein were causing the two distinct peaks that the researchers observed, they used a model that allows them to simulate the dynamical movement of the protein and then create expected spectra from these states. From this simulation, they were able to determine that the shift in energy they observed was due to the presence of an ion at the gate or not. The ion adds more weight to the bond, thus changing the energy with which it vibrates. From this determination the researchers were then able to compile all their data to determine what percentage of the time the gates were occupied.

This article takes a complex technique, 2DIR spectroscopy, and utilizes it to study a complex biological molecule. They show the power this technique can have to resolve how often a potassium gate is open or closed, and how the two gates can influence each other to open or close.

 

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