November/December Paper of the Month – The temple of the mind
07/07/10 Portland, OR
The School of Medicine newsletter spotlights a recently published faculty research paper in each issue. The goal is to highlight the great research happening at OHSU and to share this information acrosslarge departments, institutes and disciplines. A list of all papers compiled by the OHSU Library and published by OHSU faculty during the prior month (in this case, two months since this is a double Nov/Dec issue) is also provided here.
This month's featured paper was published in Nature: "X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor," by Alexander I. Sobolevsky, Michael P. Rosconi and Eric Gouaux. Eric Gouaux, PhD, is a Senior Scientist at the Vollum Institute and a Howard Hughes Medical Institute Investigator.
The paper summary below was compiled by Associate Dean for Basic Science Mary Stenzel-Poore and reviewed by Dean Mark Richardson and Vice President/Senior Associate Dean for Research Dan Dorsa.
A scientific team lead by Dr. Gouaux has solved the structure of one of the most important receptors in the brain — the ionotropic glutamate receptor known as GluA2. The importance of this work for understanding how this receptor binds its ligands and opens and closes the ion channel cannot be overstated. This structure will serve as a template for the entire family of glutamate receptors.
Published in the December 10 issue of Nature (log-in may be required), the authors reported the 3-dimensional crystal structure of the AMPA-sensitive rat GluA2 receptor. The group determined the structure of this homo-tetrameric transmembrane spanning receptor at 3.6 Angstrom resolution in complex with a competitive antagonist bound to the ligand binding site.
Their findings provide valuable insight into how this receptor is configured on the cell's surface to bind glutamate and trigger the opening of the ion channel. Their studies tell us that the receptor is Y-shaped with three parts — the top with two symmetric prongs and just below this is the ligand binding domain which controls the opening of the ion channel, which itself is shaped like a Mayan temple with 4-fold symmetry and a broad cytoplasmic base. This structural information allows new and important interpretations of studies that have been performed over the past two decades on the pharmacology and functional outcomes of receptor activation among this family of receptors.
Knowing the architecture of this receptor will help scientists understand the structure of other members of this ionotropic receptor family and, most importantly, will define the molecular underpinnings of receptor activation and dysfunction in the setting of neurodegeneration and chronic disease states such as Alzheimer's and epilepsy.
Click here for the summary by Nature News and here for the Oregonian article.