Glutamate transporter homolog
Pyrococcus horikoshii OT3 (archaea)
Neurons are cells that can communicate with each other or send signals to other types of cells. They form the nervous system of an organism. The human brain for instance contains more than 100 billion neurons. A neuron signals to other cells by releasing a special kind of chemical, called a neurotransmitter, at the junction between the two cells, the synapse. The neurotransmitter then propagates to the membrane of the receiving cell, where it binds to special receptor proteins. As a result of this, ion channels in the receiving cell's membrane open and ions pass the membrane, altering the transmembrane electrostatic potential. Glutamic acid is a neurotransmitter used at the excitatory synapses. These synapses are responsible for learning and memory. If excessive amounts of glutamic acid are not removed from the synapse area after the signal transmission, various nervous system malfunctions and breakdowns like schizophrenia and epilepsy occur. Glutamate transporters are membrane proteins responsible for the intake of this residual glutamic acid.
The crystal structure of one such transporter, shown here, provides us with a possible mechanism for this process. The glutamate transporter is a trimer, whose extracellular portion has the shape of a wide bowl. The surface of this bowl is highly hydrophilic, and permits easy access for glutamate molecules to the three substrate binding sites at its bottom, almost halfway across the membrane bilayer. After binding, the substrate gets enclosed between two helical hairpins, HP1 and HP2. HP1 rearranges and opens a pathway for the substrate to leave into the cytoplasm while HP2 keeps its original position of blocking the binding site from the cell's exterior. After the glutamic acid is released, HP1 flips back to protect the binding site from the cytoplasm. Additional rearrangements occur, HP2 opens up the binding site to the synaptic area, and the transporter is ready for the next molecule. A modified version of this transporter, found in rat tongues, is the taste receptor for umami, which is one of the five tastes, along with salty, sweet, bitter and sour. Salts of glutamic acid, like monosodium glutamate (MSG), are used as flavor enhancements in processed foods, and can also be found in protein contained in processed meat and cheese.
Protein Data Bank (PDB)
Yernool, D. Boudker, O. Jin, Y. Gouaux, E.; "Structure of a glutamate transporter homologue from Pyrococcus horikoshii"; Nature; (2004) 431:811-818 PubMed:15483603.
author: Rossen Apostolov