User heads for Stockholm

The ESRF has made a key contribution to GPCR structures, which offer important new approaches to drug development, because it was the first  synchrotron to offer micro-focus X-ray beams.

A key result leading up to Kobilka and Lefkowitz’s SEK 8 m award was obtained at the ESRF in 2007, when Kobilka and colleagues solved the first GPCR that binds to hormones or neurotransmitters. Using the ESRF’s ID13 and ID23-2 beamlines, Kobilka’s group, in collaboration with Gebhard Schertler and colleagues at the MRC Laboratory of Molecular Biology (LMB) in Cambridge, UK, determined the structure of the beta-two adrenergic receptor, β2AR. “I have a very fond memory of the ESRF,” Kobilka told ESRFnews last year. 
Schertler, who is now at the Paul Scherrer Institute in Switzerland, says several others were in the running for the Nobel prize. “In the end it was awarded for the adrenergic receptor, rather than for pioneering GPCR structure studies, so the award is very well deserved,” he told ESRFnews. “Of course it would be wonderful if I had got the prize, but Brian Kobilka is a great collaborator, and in a way I am glad not to have the burden that the Nobel prize can bring.”

The ESRF results paved the way to Kobilka’s next seminal achievement in 2011, obtained using the Advanced Photon Source near Chicago. Here, his team captured an image of the β2 receptor activating a G protein, which is the key event in how a hormone binding to the outside of a cell eventually causes chemical changes within the cell.

“The thing that sets Brian apart from the rest of us is the beautiful structure of the β2 receptor bound to a G protein and his work in developing GPCR-T4 lysozyme fusions,” says Chris Tate of the LMB, who has made similar breakthroughs in understanding the sister structure β1AR using the ESRF, also in collaboration with Schertler. “His prize is richly deserved and it is also a fantastic recognition for the whole of the field, because there are hundreds more GPCR structures to be determined.”

This article originally appeared in ESRFnews, December 2012. 

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Top image: Brian Kobilka in the limelight after the Nobel prize announcement. (Photo credit: L A Cicero/Stanford News Service).