Wednesday, October 10, 2012

The 2012 Nobel Prize in Chemistry

Today the 2012 Nobel Prize in Chemistry was awarded to Robert Lefkowitz and Brian Kobilka for their work on G protein-coupled receptors.

How do signals from outside the cell get transmitted into the cell? It's a question that long plagued scientists and the answer underlies many if not all vital cellular processes. It was thought that there were protein receptors on the surface of the cell that recognized molecules and in the process of this recognition, specific events were triggered inside the cell - the action of the hormone adrenaline, for example. In the 1960's Lefkowitz's lab used radioactive hormones to isolate the receptor responsible for the action of adrenaline - the B2 adrenergic receptor. This initial step of isolating the receptor was key in allowing scientists to characterize the biochemical properties of the protein. Isolation of the protein in an active form was not trivial since the receptor had portions outside the cell, portions in the membrane of the cell, and portions inside the cell - it is a transmembrane protein.

In the 1980's Kobilka joined Lefkowitz's lab and set out trying to isolate the gene encoding the B2 adreneric receptor. He was successful and when they analyzed the gene sequence, they realized there were other similar genes - thereby implicating a gene family. As it turns out, there are many genes that encode these protein receptors, all similar in function, but differing in what external signal they recognize and transmit inside the cell. - smell, light, histamine (think allergies), mood, appetite and sleep (serotonin).

Kobilka left Lefkowitz's lab and established his own research group studying these receptors - especially trying to determine their molecular structure. In the last couple of years, his group succeeded in solving the structure of the B2 adrenergic receptor just as a hormone has bound giving new intricate details on how these important signal is transmitted to the cell.

It is suggested that more than half of all drugs act on this family of G protein-coupled receptors highlighting the importance of understanding exactly how these proteins function and opening doors for the treatment of many disorders.

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