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 Numbers count in the genetics of moles and melanomas
16.08.2019 | University of Queensland

nachricht Working out why plants get sick
16.08.2019 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

Im Focus: Scientists create the world's thinnest gold

Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.

The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...

Im Focus: Study on attosecond timescale casts new light on electron dynamics in transition metals

An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.

The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Graphene nanoflakes: a new tool for precision medicine

19.08.2019 | Health and Medicine

Working out why plants get sick

16.08.2019 | Life Sciences

Newfound superconductor material could be the 'silicon of quantum computers'

16.08.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>