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Researchers get a grip on nervous system's receptors
Date:2/7/2011

A digital signal processing technique long used by statisticians to analyze data is helping Houston scientists understand the roots of memory and learning, Alzheimer's and Parkinson's diseases and stroke.

Researchers at Rice University and the University of Texas Health Science Center at Houston (UTHealth) reported today in the journal Nature Chemical Biology that single molecule fluorescence resonance energy transfer (FRET) techniques combined with wavelet transforms have given them a new view of the AMPA receptor, a glutamate receptor and a primary mediator of fast signal transmission in the central nervous system.

Scientists have long thought these receptor proteins, which bind to glutamate to activate the flow of ions through the nervous system, are more than simple "on-off" switches. A "cleft" in the AMPA protein that looks and acts like a C-clamp and that binds the neurotransmitter glutamate may, in reality, serve functions at positions between fully open (off) and fully closed (on).

"In the old days, the binding was thought to be like a Venus flytrap," said Christy Landes, a Norman Hackerman-Welch Young Investigator Assistant Professor of Chemistry at Rice and lead author of the new paper. "The trap sat there waiting for something to come into the cleft. A neurotransmitter would come in and -- oops! -- it snapped shut on the molecule it was binding to, the gate opened up and ions would flow. We have all sorts of high-quality X-ray crystallography studies to show us what the snapped-open and snapped-shut cleft looks like."

But X-ray images likely show the protein in its most stable -- not necessarily its most active -- conformation, she said. Spectroscopy also has its limits: If half the proteins in an assay are open and half are shut, the measured average is 50 percent, a useless representation of what's really going on.

The truth, Landes said, is that the clefts of AMPA receptors are constantly open
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Contact: David Ruth
druth@rice.edu
713-348-6327
Rice University
Source:Eurekalert

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