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Scripps Research scientists pinpoint shape-shifting mechanism critical to protein signaling
Date:9/6/2011

JUPITER, FL, September 6, 2011 In a joint study, scientists from the California and Florida campuses of The Scripps Research Institute have shown that changes in a protein's structure can change its signaling function and they have pinpointed the precise regions where those changes take place.

The new findings could help provide a much clearer picture of potential drugs that would be both effective and highly specific in their biological actions.

The study, led by Patrick Griffin of Scripps Florida and Raymond Stevens of Scripps California, was published in a recent edition of the journal Structure.

The new study focuses on the β2-adrenergic receptor, a member of the G protein-coupled receptor family. G protein-coupled receptors convert extracellular stimuli into intracellular signals through various pathways. Approximately one third of currently marketed drugs (including for diabetes and heart disease) target these receptors.

Scientists have known that when specific regions of the receptor are activated by neurotransmitters or hormones, the structural arrangement (conformation) of the receptor is changed along with its function.

"While it's accepted that these receptors adopt multiple conformations and that each conformation triggers a specific type of signaling, the molecular mechanism behind that flexibility has been something of a black box," said Griffin, who is chair of the Scripps Research Department of Molecular Therapeutics and director of the Scripps Florida Translational Research Institute. "Our findings shed significant light to it."

The study describes in structural detail the various regions of the receptor that are involved in the changes brought about by selective ligands (ligands are molecules that bind to proteins to form an active complex), which, like a rheostat, run the gamut among activating the receptor, shutting it down, and reversing its function, as well as produ
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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