Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Versatile Switch for Light-Controlled Cells

09.04.2015

Scientists from Jülich, Grenoble, Frankfurt and Moscow uncovered the atomic structure of KR2, a light-driven transporter for sodium ions which had only recently been discovered. Based on the structural information the team then identified a simple way to turn KR2 from a sodium- into a potassium pump using simple means.

Integrated into neurons, this could make KR2 a valuable tool for optogenetics, a new field of research that uses light-sensitive proteins as molecular switches to precisely control the activity of neurons and other electrically excitable cells using light impulses. The findings have been published in the journal Nature Structural and Molecular Biology.


The surface of the KR2 complex shown from the side. Each of the five KR2 molecules binds and transports a sodium ion (purple) across the membrane. The light-sensitive retinal inside the complex, which regulates pumping activity, is transparent.

Copyright: Forschungszentrum Jülich/IBS Grenoble


Left: Like all protein molecules, the KR2 pump consists of a single chain of amino acids folded into complex three-dimensional structure. Seven connected helices (yellow) form a channel inthe cell membrane through which sodium ions are transported. 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

In 2013, scientists made an unexpected discovery while investigating the marine bacterium Krokinobacter eikastus. In its cellular membrane, the bacterium had a previously unknown type of ion transporter. The protein, which was dubbed KR2, belongs to a group of light-sensitive proteins that have become the basis of the research field of optogenetics.

When exposed to light, these proteins allow charged particles to flow into the cell or transport them outside the cell. Integrating these ion transporters into the neuronal membrane makes it possible to alter their state of charge using light impulses, thus enabling their activity to be precisely controlled. This method quickly became established in the neurosciences, in particular. However, only a few proteins are currently available for this and each of these proteins was only permeable to certain ions.

KR2 transports positively charged sodium ions out of the cell, which is a feature that so far had been missing in the toolkit of optogenetics. However, until now neither the exact atomic structure nor the ion transport mechanism had been known – which is an important prerequisite for utilizing KR2 and adapting it for specific applications.

This challenge awakened the interest of a team of structural biologists headed by Prof. Valentin Gordeliy, who heads research groups at the Institute of Complex Systems (ICS-6) at Forschungszentrum Jülich, Germany, at the Institute de Biologie Structurale in Grenoble, France, and at the Moscow Institute of Physics and Technology in Russia.

Using X-ray crystallography, the team obtained the first high-resolution 3D structural images of the single protein and the five-part complex that the KR2 molecule spontaneously forms under physiological conditions.

"The structure of KR2 has many unique features," says Ivan Gushchin, one of the lead authors of the study and a postdoc of Gordeliy. One of these features is a short protein helix capping the outfacing opening of the pump like a lid. A feature of KR2, that the scientists were particularly interested in was the unusual structure of the inward facing ion-uptake cavity, which was found to be unusually 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 explains.

To put this idea to the test, Gordeliy´s team changed the structure by swapping specific amino acids at the site in question through targeted mutations. Not only did KR2 indeed lose its sodium-pumping ability; but also one of the mutations seemed to turn KR2 into a light-driven potassium pump – the first of its kind.

To accurately prove this observation the team performed a series of electrophysiological experiments with the purified protein in collaboration with Ernst Bamberg at the Max Planck Institute of Biophysics in Frankfurt am Main, who is an expert on membrane proteins and one of the founders of optogenetics.

For potential optogenetic application, this result is especially interesting, says Bamberg: "In neurons, transporting potassium ions from the cell is the natural mechanism of deactivation. 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."

This would make KR2 a very effective off-switch for neurons. Now, ways of integrating the pump into different types of cells need to be developed. "In combination with the light-activated Channelrhodopsin 2, which is used in labs worldwide as a molecular off-switch, the KR2 potassium pump would then form a perfect pair of tools for the precise control of nerve cell activity," says Bamberg.

Original publication:
Ivan Gushchin, Vitaly Shevchenko, Vitaly Polovinkin, Kirill Kovalev, Alexey Alekseev, Ekaterina Round, Valentin Borshchevskiy, Taras Balandin, Alexander Popov, Thomas Gensch, Christoph Fahlke, Christian Bamann, Dieter Willbold, Georg Büldt, Ernst Bamberg& Valentin Gordeliy:
Crystal structure of a light-driven sodium pump. Nature Structural & Molecular Biology (2015) doi:10.1038/nsmb.3002

Contact:

Prof. Dr. Valentin Gordeliy
Institute for Complex Systems, Structural Biochemistry (ICS-6)
Forschungszentrum Jülich
Institute de Biologie Structurale (CEA-CNRS-UJF), Grenoble
Tel: +49 2461 61-9509
E-Mail: g.valentin@fz-juelich.de, valentin.gordeliy@ibs.fr

Prof. Dr. Ernst Bamberg
Max Planck Institute of Biophysics, Frankfurt am Main
Tel:+49 69 6303-2000
E-Mail: secretary-bamberg@biophys.mpg.de

Press Contact:

Peter Zekert
Institute of Complex Systems, Strukturbiochemie (ICS-6)
Tel.: +49 (0) 2461 61-9711
E-Mail: p.zekert@fz-juelich.de

Weitere Informationen:

http://www.fz-juelich.de/SharedDocs/Pressemitteilungen/UK/EN/2015/15-04-09kr2-pu... Press release and images

Annette Stettien | Forschungszentrum Jülich

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>