Have you got a light? Protein illumination

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  • Published: Apr 15, 2015
  • Author: David Bradley
  • Channels: X-ray Spectrometry
thumbnail image: Have you got a light? Protein illumination

Neuronal toolbox

A structure unique among light-activated ion pumps is the additional short helix (blue) capping the outside opening of the pump like a lid. The pumping activity is driven by the small light-responsive retinal (green). Right: Under physiological conditions, five KR2 molecules spontaneously form a star-shaped pentameric complex. Copyright: Forschungszentrum Jülich/IBS Grenoble

An X-ray crystal structure of the protein KR2, a light-driven transporter for sodium ions, could facilitate the field of optogenetics where neurons and other electrically excitable cells can be controlled using light impulses.

In 2013, researchers discovered unexpectedly a membrane protein in the marine bacterium Krokinobacter eikastus that represented a new type of ion transporter. Now, a team from Jülich, Grenoble, Frankfurt and Moscow have obtained the structure of this protein, KR2, and have now found a facile way to convert KR2 into a potassium pump rather than a sodium pump. The team suggests that the modified protein integrated into a neuron could be used as a switch for the cell.

There is now a smalls clutch of light-responsive proteins that are the focus of and the basis of the research field of optogenetics. When exposed to light, these proteins carry ions into the cell or transport them out. The ability of KR2 to naturally transport sodium and now synthetically to transport potassium adds a useful new tool to the optogenetics toolbox.

Potassium pump

Valentin Gordeliy leads research groups at the Institute of Complex Systems (ICS-6) at Forschungszentrum Jülich, Germany, at the Institute de Biologie Structurale in Grenoble, France, and closely co-operates with his former laboratory at the Moscow Institute of Physics and Technology in Russia. He and his colleagues now have in hand the X-ray structure of the single protein and the pentamer that spontaneously self assembles from five KR2 molecular units under physiological conditions.

"The structure of KR2 has many unique features," explains one of Gordeliy's post-doctoral researchers, Ivan Gushchin. One of these features is a short protein helix capping the outfacing opening of the pump like a lid. The researchers were particularly interested in the unusual structure of the inward facing ion-uptake cavity of KR2, which was shown to be rather large and protruding from the protein surface. "We hypothesized that this structure could act as a kind of filter causing the selectivity of KR2 for sodium ions," Gushchin adds. Thus, by swapping specific amino acids at that site through targeted mutation, the team could disable the sodium-pumping function or with another mutation switch KR2 into a light-driven potassium pump. The first such protein of its kind.

Mutant KR2

To demonstrate that the mutant KR2 was indeed working as they hoped the team carried out precise electrophysiological experiments with the purified protein in collaboration with membrane protein expert and optogenetics pioneer Ernst Bamberg at the Max Planck Institute of Biophysics in Frankfurt am Main. Bamberg hints at the potential of this modified protein: "In neurons, transporting potassium ions from the cell is the natural mechanism of deactivation," he says. "Normally, an activated neuron will release them through passive potassium channels in the membrane. With a light-activated, active potassium pump this process could be precisely controlled."

The next step is to develop the techniques to integrate the potassium pump into different types of cells. The protein could then be used in combination with well-known and widely used light-activated Channelrhodopsin 2 - a molecular off-switch. Bamberg suggests that these two "would then form a perfect pair of tools for the precise control of nerve cell activity."

Related Links

Nature Struct Mol Biol 2015, online: "Crystal structure of a light-driven sodium pump"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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