Nobel Prize in Chemistry for key protein receptor discovery

By Tim Dean
Thursday, 11 October, 2012

It’s a clear example of the increasing overlap between scientific disciplines when the Nobel Prize in Chemistry goes to two researchers investigating a family of proteins that regulate biological function.

Robert Lefkowitz and Brian Kobilka have received the Nobel gong for their pioneering work in revealing the structure and function of a family of proteins known as G-protein–coupled receptors.

The proteins are significant because they perform a crucial function in allowing other molecules to pass through the cellular membrane, effectively allowing signals about the outside environment to be received within the cell itself.

Such cellular messaging is central to many processes, such as smell, vision, taste as well as a host of interactions within the body.

In 1968, Lefkowitz was investigating the receptors on the surface of cells by attaching radioactive isotopes to various hormones and then tracking where they landed on the cell, thus indicating the site of a receptor for that hormone.

Robert J. Lefkowitz taking part in the Nobel Symposium '3M: Machines, Molecules and Mind' in Stockholm, Sweden, May 2011. (Copyright © The Nobel Foundation 2011. Photo: Orasisfoto)Robert J. Lefkowitz taking part in the Nobel Symposium '3M: Machines, Molecules and Mind' in Stockholm, Sweden, May 2011. (Copyright © The Nobel Foundation 2011. Photo: Orasisfoto)

Using this process he identified several receptors, including the β-adrenergic receptor which is partnered with adrenalin.

The next breakthrough came in the 1980s when working with Kobilka, with the team isolating the gene that codes for the β-adrenergic receptor.

What they found when they pinpointed this gene was revealing. It turned out that the receptor was similar to many others, including the one in the eye that captures light.

This suggested there was a whole family of receptors – the G-protein–coupled receptors – that function in a similar manner.

This discovery changed the way we understand cellular communication and raised the prospect of targeting these receptors with drugs to treat disease. In fact, about half of all medications achieve their effect through G-protein–coupled receptors.

Robert J. Lefkowitz is based at the Howard Hughes Medical Institute and Duke University Medical Center, in the USA, and Brian K. Kobilka is based at Stanford University School of Medicine.

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