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Unprecedented detail of intact neuronal receptor offers blueprint for drug developers
Date:8/26/2014

Argonne, Ill. Scientists succeeded in obtaining an unprecedented view of a type of brain-cell receptor that is implicated in a range of neurological illnesses, including Alzheimer's disease, Parkinson's disease, depression, schizophrenia, autism, and ischemic injuries associated with stroke.

The team of biologists at Cold Spring Harbor Laboratory used the U.S. Department of Energy's Advanced Photon Source at Argonne National Laboratory to get an atomic-level picture of the intact NMDA (N-methyl, D-aspartate) receptor should serve as template and guide for the design of therapeutic compounds.

The NMDA receptor is a massive multi- subunit complex that integrates both chemical and electrical signals in the brain to allow neurons to communicate with one another. These conversations form the basis of memory, learning, and thought, and critically mediate brain development. The receptor's function is tightly regulated: both increased and decreased NMDA activities are associated with neurological diseases.

Despite the importance of NMDA receptor function, scientists have struggled to understand how it is controlled. In work published recently in Science, CSHL Associate Professor Hiro Furukawa and Erkan Karakas, Ph.D., a postdoctoral investigator, use a type of molecular photography known as X-ray crystallography to determine the structure of the intact receptor. Their work identifies numerous interactions between the four subunits of the receptor and offers new insight into how the complex is regulated. The X-ray work was done with the National Institute for General Medical Sciences and National Cancer Institute Collaborative Access Team (GM/CA) beamline at the APS and a beamline at SPring 8.

"Previously, our group and others have crystallized individual subunits of the receptor just fragments but that simply was not enough," says Furukawa. "To understand how this complex functions you need to see it all together, fully asse
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Contact: Tona Kunz
tkunz@anl.gov
630-252-5560
DOE/Argonne National Laboratory
Source:Eurekalert

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