Episodic ataxia type 6 is a rare neurological disorder that affects only a small number of individuals globally. It leads to temporary loss of muscle coordination and is caused by a mutation that alters a single amino acid in a protein responsible for transporting the neurotransmitter glutamate acro
Illustration of the glutamate transporter in neural cells , with glutamate and anions in yellow and orange. Credit: A. Guskov, University of Groningen
Professor Albert Guskov, lead author of the paper in Nature Communications on the effect of a single mutation in a glutamate transport protein in neural cells. This mutation causes the neurological disease Episodic Ataxia type 6. Credit: University of Groningen Since the human transport protein is difficult to study in the lab, Guskov and his colleagues used an analogous protein from archaea, an ancient form of unicellular organism.
Using cryo-electron microscopy on normal and mutated proteins placed in lipid nanodiscs, the team was able to compare the shape of the mutated protein to the normal version. In previous studies, the team had shown that part of the protein moves up and down through the membrane, much like an elevator. The hypothesis was that the mutation would cause the transmembrane kink in the protein to disappear, and that this would change the protein’s shape and block the elevator movement.
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