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Scripps Research team discovers new details about medically important protein family
Date:3/10/2011

LA JOLLA, CA March 10, 2011 Scientists from The Scripps Research Institute have determined a new structure from a medically important superfamily of proteins. The structure should help instruct the design of a new kind of therapeutics for conditions ranging from Parkinson's disease to inflammation.

The study, published on March 10, 2011, in Science Express, an advance, online publication of selected research from the journal Science, provides important insights into how this large family of proteins, called G protein-coupled receptors (GPCRs), can recognize and respond to a wide array of signals, including odors, hormones, neurotransmitters, and light.

Many drugs, including allergy and heart medication and drugs for Parkinson's and Huntington's disease, target GPCRs, a family of proteins that comprises some 700 to 1,000 members.

A Surprisingly Stable Active Form

GPCRs sit in the cell membrane and sense various molecules outside cells. When certain molecules bind to them, the receptor's structure shifts so that it transmits its signal within the cell. These receptor-activating molecules are referred to as agonists. But GPCRs can also bind "antagonists," compounds that block the receptors' activity by preventing agonists from binding.

Up until now, researchers had primarily been able to obtain the structures of GPCRs bound to antagonistsin other words, in their inactive but more stable forms. Some scientists thought a receptor bound to an agonist would be too dynamic without stabilizing mutations or G-proteins bound for the receptor to be amenable to forming crystals, a critical step required for determining protein structures using the technique of X-ray crystallography.

In the new study, Fei Xu, a graduate student in the Stevens lab and the first author of the paper, proved these assumptions inaccurate.

The Stevens lab obtained the structure of the human A2A adenosine rec
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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