Nobel Prize 2012 in Chemistry for Studies of G-Protein-Coupled Receptors

October 12, 2012

On October 10th 2012, The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2012 to Robert J. Lefkowitz and Brian K. Kobilka for studies of G-protein-coupled receptors.

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 (GPCR).

Smart receptors on cell surfaces

An illustration shows the crystal structure of an activated beta-adrenergic receptor, as mapped out by Brian Kobilka and his colleagues. The study of how G-protein-coupled receptors and how they work with such substances as adrenaline earned Kobilka and Robert Lefkowitz the Nobel Prize for chemistry (© NobelPrize.org).

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

Robert J. Lefkowitz (© Chris Hildreth, Duke Photography)

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.

www.lefkolab.org

Listen to a telephone interview with Robert J. Lefkowitz following the announcement of the 2012 Nobel Prize in Chemistry, 10 October 2012. The interviewer is Adam Smith, Editorial Director of Nobel Media or read the interview (© Nobel Media AB 2012).

Video: Robert Lefkowitz celebrating the 2012 Nobel Prize in Chemistry

Brian J. 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.

http://med.stanford.edu/kobilkalab

Listen to a telephone interview with Brian J. Kobilka following the announcement of the 2012 Nobel Prize in Chemistry, 10 October 2012. The interviewer is Adam Smith, Editorial Director of Nobel Media or read the interview (© Nobel Media AB 2012).

Video: Brian J. Kobilka celebrating the 2012 Nobel Prize in Chemistry

 

Background information

Scientific background:
Studies of G-protein-coupled receptors

Basic information:
Cells and sensibility

The Royal Swedish Academy of Sciences is responsible for the selection of the Nobel Laureates in Chemistry from among the candidates recommended by the Nobel Committee for Chemistry. The Nobel Committee is the working body that screens the nominations and selects the final candidates for the Nobel Prize in Chemistry. It consists of five members, but for many years the Committee has included adjunct members with the same voting rights as members.

Nobel Prize® is the registered trademark of the Nobel Foundation

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