The ESRF congratulates its user Brian Kobilka on the Nobel Prize

10-10-2012

Brian Kobilka and Robert Lefkowitz are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of G-protein–coupled receptors (GPCR). In 2006-2007, Kobilka and his colleagues solved a key GPCR structure at the ESRF that is highlighted in the Nobel Prize announcement.

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GPCRs are tiny proteins embedded in cellular membranes that spring into action when molecules from inside or outside the body pass by, activating G-proteins inside the cell and triggering a physiological response. Some set off the retina’s reaction to light and the nose’s response to odours, while others bind to the hormones and neurotransmitters that regulate our moods or affect the strength of our heartbeat. In a nutshell, these proteins allow our cells to communicate. However, solving the structure of GPCRs was for many years considered an unsurmountable challenge as these proteins are only available in minute quantities, are unstable when removed from their cellular environment and continually undergo conformational “wobbles”. 

After scientists had succeeded to grow GPCR crystals, synchrotrons like the Advanced Photon Source (APS) near Chicago, US and, in particular, the ESRF and its automated microfocus beamlines were vital to extract useful diffraction data from the tiny crystals.

The first structural solution of a human GPCR was rhodopsin, in 2000, followed by a second structure in a different crystalline arrangement at the ESRF in 2004. It was in 2007 when Kobilka solved the first GPCR that binds to hormones or neurotransmitters. Using the ESRF’s ID13 and ID23-2 microfocus beamlines, his group at Stanford University in the US 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 the ESRF in 2011. “Gebhard (Schertler) brought us to the beamline in 2005 to test our first crystals and again in 2006 and 2007 to collect data that led to the first β2AR structure.” This paved the way to Kobilka's achievement in 2011 called by the Nobel Foundation “another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell”.

Today, everybody at the ESRF congratulates Brian Kobilka, his team at Stanford University and his co-workers around the world who took part in his research, for the Nobel Prize 2012.

A year ago, on 24 August 2011, Nature News published a detailed account on how synchrotrons have helped Kobilka and his colleagues, including from MRC Cambridge, to solve the structure of the beta-two adrenergic receptor:

http://www.nature.com/news/2011/110803/full/476387a.html

Top image: Crystal structure of activated beta-2 adrenergic receptor β2AR (red) in complex with G-proteins (green, cyan and yellow). Credit: S.G.F. Rasmussen et al., Nature 477, 549–555 (2011).