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Tuesday, July 30, 2013

Nobel Prize in Chemistry 2012 for G Protein Coupled Receptors

After a long hiatus, I'm back to blogging about a Nobel Prize that matters very much to me. Nobel Prizes, as its founder Alfred Nobel puts it in his will, aims to reward people for making great contributions without regard to race and nationality.

The Nobel Prize in Chemistry rewards scientists for contributing to the field of chemistry. Apart from pure chemistry, prizes are also awarded for discoveries made in molecular biosciences. The prize in chemistry has a lot to do with better medicines used to treat diseases today and chemical processes used in industry to quickly transform raw materials into finished products; in short the Nobel Prizes work touches almost every aspect of our lives. The scientists worked tirelessly in the labs and fields to make our lives better, we should give a big salute for their effort :)

Who wins the award?

Robert Lefkowitz and Brian Koblika
From left: Robert Lefkowitz and Brian Koblika

The 2012 Nobel Prize in Chemistry was jointly awarded to Robert J. Lefkowitz of Duke University and Brian K. Koblika of Stanford University.

What is it awarded for?

The prize in chemistry was awarded for work on G protein coupled receptors. Have you ever experienced the thrill of adrenaline rush? Apart from the action of the hormone adrenaline, this feeling also depends on adrenaline receptors located on surfaces of your cells.

For a long time, how cells sense their environment has been a mystery. Scientists knew that hormones like adrenaline have powerful effects like raising heartbeat and blood pressure, so they thought there must be a recipient for hormones that are located on cell surfaces. This knowledge has been hidden from us until the Robert Lefkowitz began his work in 1968.

Lefkowitz started to use radioisotope labelling on hormones to trace their corresponding receptors. Thanks to radioactivity, he managed to fish out an important receptor for adrenaline: the β-adrenergic receptor. The receptor looks like this:

seven pass receptor ribbon diagram

The receptor (blue) is a protein chain that passes the cell membrane seven times, hence it is also named seven pass receptors. At the bottom of the receptor lies a G protein consisting of three parts: α, β and γ subunits. Once the hormone molecule (yellow) binds in the pocket at the receptor, it changes the shape of the receptor.  The α subunit of the G protein complex detaches to pass the signal to other parts of the cell.

The next breakthrough came in the 1980s when Brian Koblika found the gene (DNA) in our genome that encodes the adrenaline receptor. Interestingly, they found the adrenaline receptor looks a lot like the receptor found in our eyes - the receptor that captures light that enables us to see. It turned out that seven pass receptors belongs to a very large family!

What does G protein coupled receptors have to do with me?

Today, we known that there exists at least a thousand of such receptors in humans, responsible to sense stuff like light, flavour, smell, nutrients and hormones. The seven pass architecture is highly adaptable- evolution has created and modified so many of them to bind lots of stuff in the receptor's pocket. These receptors play a very big role in our senses - they are found in our nose, tongue and eyes.

But what makes this class of receptors so important? Half of the medicines we buy in pharmacies act on G protein coupled receptors to make us feel better. By understanding how they work, for sure we can come up with better medicines :)

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