ChemFAQs: 2012 Nobel Prize in Chemistry (Translated)

Drumroll please…And the 2012 Nobel Prize in Chemistry goes to…Robert J. Lefkowitz and Brian K. Kobilka “for studies of G-protein-coupled receptors.”¹ So, why is this work so important? Well G-protein-coupled receptors (GPCRs) are the primary means by which all cells in our bodies communicate with each other. So for example, imagine that you are allergic to pollen, and you happen to breathe some in. Immune cells in your nose recognize the pollen as foreign and decide to take the “shoot first and ask questions later” policy by sounding the alarm. This “alarm” consists of a small molecule called histamine. The histamine in your system is detected by nearby cells that have histamine receptors.

These receptors fall into the large family of receptors called…Yep, you guessed it, G-protein-coupled receptors! A typical GPCR is a protein consisting of 7 helixes embedded in the cell membrane with part of the receptor sticking out of both the inside and the outside of the cell.² When histamine is detected by the GPCR outside the cell, it enters the space in the middle of the GPCR. This causes a change in the three-dimensional shape of the receptor inside the cell. The new, more open shape allows the GPCR to react with the inactive form of a G-protein called G-abg (G-alpha, beta, gamma). This reaction causes the inactive G-protein (or Guanine nucleotide-binding protein if you speak chemicalese) to break apart into smaller G-proteins called G-alpha and G-beta,gamma.³ The G-alpha piece goes on to start a chemical chain reaction in the cell that ultimately leads to your allergy symptoms. As long as the histamine is bound to the GPCR, it will continue to make more and more G-alpha (intensifying your allergy symptoms). Eventually, the histamine will be released back into your system where it can move to the next cell and continue making your day miserable. In this way, a relatively small number of histamine molecules can have a broad impact on your body.

Fortunately, bright scientists like Drs. Lefkowitz and Kobilka have figured out the structure and function of GPCRs. Armed with this knowledge, we can create molecules that bind to these receptors and prevent the bad effects that molecules such as histamine have on our bodies. Like an NBA team playing a high school team, “antihistamines” box-out the histamine by occupying the paint a.k.a. the place where histamine normally would bind to the histamine receptor. In fact, most medicines work by acting on various GPCRs throughout your body.² In essence, this research on GPCRs has fundamentally changed and expanded our understanding of how drugs work. Ultimately, this will lead to more effective treatment of diseases!