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  Latest News  
  October 18,  2004
Volume 82, Number 42
p. 13


Crystal structure hints at how brain controls levels of neurotransmitter

GATE AGENT Extracellular glutamate enters the bowl-shaped transporter (cross-section shown) via its water-filled basin. Gouaux believes that glutamate binds to each of three sites (two are shown in blue mesh) before being ushered into the cell.


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.

  Chemical & Engineering News
ISSN 0009-2347
Copyright © 2004

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