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New Model Could Bring Custom Optogenetics Proteins

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Deeper understanding of the molecular mechanisms of a light-sensitive protein could lead to more specialized optogenetics techniques.

Researchers at Ruhr University Bochum probed channelrhodopsin-2, which is already widely used in optogenetics experiments, using time-resolved Fourier-transform infrared (FTIR) spectroscopy.

“The application of channelrhodopsin-2 in optogenetics has revolutionized neurobiology in the recent years,” said professor Dr. Klaus Gerwert. “However, scientists had not been aware of what is actually happening inside a protein and thus ultimately triggers its activation.”

The EHT model of channelrhodopsin-2.
The pore of the ion channel is opened by removing the amino acid E90. Water molecules enter and tilt Helix H2, thus opening the continuous channel. Courtesy of Ruhr University Bochum.

FTIR analysis showed that light causes the amino acid E90 to move aside an open a pore in the protein.

The opening of the pore allows water to flow inside the protein, the researchers determined using molecular dynamic simulations. The entering water then tilts the protein helix H2, opening a channel for ions to flow through and activate the associated brain cell.

Originally discovered in green algae, channelrhodopsin-2 can be produced by genetically altered mammalian cells. Its properties of light sensitivity and ion conductivity have enabled experiments where test animals memories and sleep patterns altered, for instance.

Gerwert said his group’s EHT (E90-Helix2-tilt) model will enable protein engineering for specific optogenetics applications. The protein’s properties, such as which wavelengths of light it responds to, could be controlled through mutation of E90, and the conductivity or selectivity for certain ions could be customized.

The research was published in Angewandte Chemie International Edition, (doi: 10.1002/anie.201410180).

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Mar 2015
A discipline that combines optics and genetics to enable the use of light to stimulate and control cells in living tissue, typically neurons, which have been genetically modified to respond to light. Only the cells that have been modified to include light-sensitive proteins will be under control of the light. The ability to selectively target cells gives researchers precise control. Using light to control the excitation, inhibition and signaling pathways of specific cells or groups of...
Research & TechnologyEuropeGermanyRuhr University BochumKlaus GerwertBiophotonicsoptogeneticsBioScanTech PulseEuro News

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