| STRUCTURE |
In the brain, neurons communicate with their neighbors by sending out bursts of small molecules known as neurotransmitters. Researchers have now cracked the structure of a microbial relative of the transporter protein that controls levels of glutamate, the most abundant neurotransmitter. Neurons release glutamate in response to electrical impulses. Neighboring neurons detect the surge in glutamate and convert the message back into an electrical signal. For such signaling to continue, the glutamate must be cleared soon after it's released into the extracellular space. That job falls to a family of membrane proteins known as glutamate transporters. Because of the technical difficulties of crystallizing a human glutamate transporter, structural biologists Eric Gouaux, Dinesh Yernool, Olga Boudker, and coworkers at Columbia University turned to a heat-stable microbial relative identified by its similar sequence. The team's 3.5-Å structure--the first of any neurotransmitter transporter--hints at how the ones in humans work [Nature, 43, 811 (2004)]. The trimeric transporter is bowl shaped, with a water-filled extracellular basin that dips nearly halfway across the membrane bilayer. At the bottom of the basin, three pairs of helical hairpins create three glutamate-binding sites. Gouaux suggests that these hairpins act as gates that allow alternating access to either the extracellular or intracellular side of the membrane. Such a mechanism is necessary to prevent glutamate, which is present at much higher levels inside neurons than outside, from simply rushing down its concentration gradient and flooding the extracellular space. Gouaux hopes that structures of the transporter in other functional states will reveal the conformational changes required for glutamate transport. |
| AUTHOR | structural biologists Eric Gouaux, Dinesh Yernool, Olga Boudker, and coworkers at Columbia University |
| LITERATURE REF. |
[Nature, 43, 811 (2004)]. |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |