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The complete structure of the glutamate receptor, an extremely complicated and important brain protein, was reported in the journal Nature on November 29.
Eric Gouaux, a protein crystallographer at Oregon Health and Science University, and colleagues studied the rat glutamate receptor GluA2. Glutamate receptors act as relays in the central nervous system and are also thought to be critical in memory and learning. When the neurotrasmitter glutamate binds to the protein an ion channel is opened in the neuronal membrane. Ions flow across the membrane, transmitting an electrical pulse down the nerve.
The structure was determined using x-ray crystallography. Researchers grew a crystal of the many receptors, a very challenging process, and exposed it to x-rays. To facilitate crystallization, the protein was studied in the channel-closed form. By analyzing how the x-rays were reflected, an atomic-level structure of a single protein was determined. The GluA2 receptor is shaped like the capital letter Y and has three main sections. The top of the protein is two prongs followed by the area where glutamate binds to the receptor to open the ion channel. The bottom of the protein is the ion channel itself. The receptor is made of four subunits that are chemically identical, but folded differently.
The full structure of a glutamate receptor has never been seen until now. Knowing the full structure of the receptor will allow scientists to better understand how it functions, as well as facilitate the design of drugs that bind to the receptor. "If you know what the lock looks like then you can better design a key," says Gouaux. "If you don't know you're at a loss." This research has important implications for those trying to design therapies for diseases where something goes wrong with the glutamate receptors, such as Alzheimer's and epilepsy. [Nature]
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