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

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Stevens began working on the structures of GPCRs more than two decades ago. His group in collaboration with researchers at Stanford University solved the first human GPCR structure, the β2 adrenergic receptor, in 2007a project that took 17 years to complete. Since then the Scripps Research team has been successful in obtaining several other GPCR structures in collaboration with other laboratories around the world.

"The reason we have now solved several human GPCR structures is the strong and robust scientific platform we built at Scripps with NIH support," says Stevens, who is director of the NIH Common Fund Joint Center for Innovative Membrane Protein Technologies, focused on developing and disseminating technologies, and the National Institute of General Medical Sciences PSI:Biology GPCR Network, focused on increasing the knowledge of GPCR biology. "When the NIH funded this research they took a very big chance on high risk/high reward science and it is now paying off in multiple ways from new technologies to new biological insight."

Like all proteins, GPCRs consist of long chains of amino acids that assemble themselves in three-dimensional shapes. GPCRs consist of seven helices that span the membrane of a cell. Loops connecting the helices sit both outside the cell membrane and inside the cell.

In the new study, Stevens and colleagues found that when the agonist bound the A2A receptor, helices 5, 6 and 7 underwent a dramatic shift in their positions. In contrast, helices 1 to 4 tended to stay relatively still. "GPCRs appear to be composed of two domains," he explained. "The first four helices appear more rigid than the last three."

In addition, the portions of the receptor sitting outside the cell membrane shifted their positions to accommodate the agonist binding, whereas the segments on the inside of the cell had smaller changes.

The greater flexibility for the outside portions may hold the
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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