The 2012 Nobel Prize in Chemistry was awarded jointly to Robert J. Lefkowitz and Brian Kobilka for studies of G-protein-coupled receptors, which are the portals by which information about the environment reaches the interior of cells and leads to their responses. About half of all drugs work by interacting with G-protein-coupled receptors.

The official Nobel Prize press release:

10 October 2012

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2012 to

Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA

and

Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA

"for studies of G-protein–coupled receptors"

Smart receptors on cell surfaces

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein–coupled receptors.

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein–coupled receptors.

The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein–coupled receptors function. Furthermore, in 2011, Kobilka achieved 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. This image is a molecular masterpiece – the result of decades of research.

Robert J. Lefkowitz, U.S. citizen. Born 1943 in New York, NY, USA. M.D. 1966 from Columbia University, New York, NY, USA.Investigator, Howard Hughes Medical Institute. James B. Duke Professor of Medicine, and Professor of Biochemistry, Duke University Medical Center, Durham, NC, USA.

Brian K. Kobilka, U.S. citizen. Born 1955 in Little Falls, MN, USA. M.D. 1981 from Yale University School of Medicine, New Haven, CT, USA. Professor of Medicine, and Professor of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

Also see:

Cell Signalling Caught in the Act and Cell Signalling: It's All About the Structure, both by Lizzie Buchen

And videos of two 2010 Lefkowitz lectures:

Part 1 Seven Transmembrane Receptors

Part 2 Beta-arrestins