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Molecular movements of neural transporters unveiled
Date:4/25/2011

llowing neurotransmitters to move back into the cell where their concentration is higher than outside. But until now, exactly how these transporters function has been a mystery.

"The transporters themselves are of enormous interest both medically and specifically to the National Institute on Drug Abuse because, fundamentally, they are essential for signaling," says one senior author, Dr. Harel Weinstein, chairman and Maxwell M. Upson Professor of Physiology and Biophysics, and director of the Institute for Computational Biomedicine at Weill Cornell Medical College. "The better we understand neuronal signaling, the better we understand brain function, disease and drug addiction."

To figure out how transporters work, it is first necessary to study their molecular structure, Dr. Weinstein says. Because these membrane proteins are so flexible and prefer lipid-rich surroundings, it is more difficult to obtain their crystal structures than those of soluble proteins or DNA. But in 2005, scientists characterized the structure of a bacterial equivalent of NSSs called the leucine transporter (LeuT). This protein is easier to analyze structurally, as it is available in large quantities and is stable because it is found in heat-loving bacteria that live in extreme environments (proteins have to be very stable and rigid to withstand high temperatures). Although LeuT transports amino acids such as leucine and alanine, rather than neurotransmitters, it closely resembles mammalian NSSs in both structure and function.

But structural analyses alone provide only snapshots of the transporter molecule. To elucidate the entire molecular sequence of LeuT action, the team performed imaging studies using single-molecule fluorescence resonance energy transfer (smFRET) under the leadership of the other senior author, Dr. Scott Blanchard, associate professor of physiology and biophysics at Weill Cornell Medical College. Unlike traditional biochemical approaches, this
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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