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Source: Forschungszentrum Julich-Jülich, November 19, 2020 – Jülich researchers have used simulations on the JURECA supercomputer and X-ray crystallography to explain how sodium ions drive the transport of glutamate in the brain. The so-called Excitatory Amino Acid Transporters, EAATs for short, are responsible for this, which remove the messenger substance glutamate from the synaptic gap between nerve cells. The article was published in the current issue of the renowned journal “Science Advances”.

Glutamate enables activating signals to be transmitted from one nerve cell to a neighboring one. So that the signal transmission stops exactly at the end of the activating signal, glutamate has to be quickly removed from the synapse after its release. This is the job of specialized proteins in the cell membrane, the EAAT glutamate transporters.Molecular dynamics simulation of the binding of sodium ions to glutamate transporters To power cells. To do this, the transporters bind the neurotransmitter glutamate on the outside of the cell together with a total of three sodium ions and transport everything together into the interior of the cell. The natural gradient in the sodium concentration, which is significantly higher outside the cell than inside, acts as a driving force. It was previously unclear how EAATs bind glutamate together with sodium ions and how the ions drive this process. The Jülich researchers have now answered this question: With the help of X-ray crystallography, it was possible to record a high-resolution structure of a sodium-bound transporter immediately before the glutamate binds with a previously unattainable accuracy. Simulations on the Jülich supercomputer JURECA and further experiments were able to show how the binding of two sodium ions enables the subsequent binding of glutamate and a third sodium ion. The results provide important insights into molecular processes of information processing in the brain and could be helpful for new treatment methods for to develop ischemic brain diseases such as stroke, in which elevated glutamate concentrations occur. Original publication: Na + -dependent gate dynamics and electrostatic attraction ensure substrate coupling in glutamate transporters, Alleva, Kovalev et al., Sci. Adv. 2020; 6: eaba9854; November 18, 2020https: //doi.org/10.1126/sciadv.aba9854 Contact person: Jun.-Prof. Jan-Philipp Machtens Institute of Biological Information Processing, Molecular and Cell Physiology (IBI-1) Tel .: 02461 61-4043 E-Mail: j.machtens@fz-juelich.de Prof. Christoph Fahlke Institute of Biological Information Processing, Molecular and Cell Physiology (IBI-1) Tel .: 02461 61-3016E-Mail: c.fahlke@fz-juelich.dePress contact: Erhard Zeiss, Press OfficerTel .: 02461 61-1841E-Mail: e .zeiss @ fz-juelich.de

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