X-Rays reveal 3-D structural image of brain receptor

Glutamate X-RayResearchers recently mapped the complete structure of a glutamate receptor, a key communications port in brain cells.  Scientists at Oregon Health and Science University (OHSU) in Portland pieced together the three-dimensional image of the protein by bombarding it with X-rays, a technology called X-ray crystallography.  Knowledge about the receptor’s form is expected to yield insights into its function in the nervous system.

Eric Gouaux, Ph.D., senior scientist at OHSU’s Vollum Institute, led the team that assembled the intricate map, which took several years of X-ray imaging.  The result was a panorama of unparalleled definition showing the AMPA-subtype of the glutamate receptor in the rat brain.  The figure, pictured at right, provides the first view of the receptor’s transmembrane region.

The X-rays also revealed a surprise: four structurally identical subunits that can shift into different arrangements.  “The finding has profound implications on the mechanism of action of this important family of receptor channels,” said Shai Silberberg, Ph.D., a program director with the National Institute of Neurological Disorders and Stroke (NINDS), which supported the research together with the Howard Hughes Medical Institute.

Receptors are proteins embedded in the neuron surface at synapses — the junctions where chemical messengers carry signals from one cell to another.  Like a lock and key mechanism, when a receptor latches onto its corresponding neurotransmitter, it changes shape to relay nerve signals down the line.

The newly mapped receptor responds to glutamate, a communications workhorse critically involved in the rapid signaling that occurs during thinking, learning and memory formation.  Scientists suspect that problems in the glutamate system play a role in epilepsy, Huntington’s disease, Parkinson’s disease, stroke and other neurological disorders.

The discoveries concerning the glutamate receptor’s structure are expected to guide future studies of related subtypes as well other classes of brain receptors.   “Time and time again Dr. Gouaux’s laboratory has solved the crystal structures of important membrane proteins involved in electrical signaling in the nervous system,” said NINDS program director Randall Stewart, Ph.D.  Such research could someday help investigators develop therapies for many neurological diseases caused by malfunctions in the glutamate system or other neurotransmitters and receptors essential for cell-to-cell communications.