Scientific Method —

Nobel prize for the heart of cell signaling

Chemistry prize for understanding how cells sense their environment.






17 Reader Comments

  1. To clarify your own explanation you should instead say that the protein is in the cell membrane. Many organisms with GPCRs (like humans) don't even have cell walls.
    9 posts | registered
  2. True. My mistake
    1498 posts | registered
  3. Dear Chris,

    unfortunately there are more mistakes in your article that seriously hinder the understanding of the great achievements by Lefkowitz and Kobilka for a reader which is not at home in the field of cell biology.
    To put things maybe more clear:
    G-protein coupled receptors (GPCRs) are transmembrane proteins, they sit in the cell membrane with one end looking to the outside, one end to the inside of the cell. Your statement that only a small part is on the outside is wrong, there are GPCRs that have huge extracellular domain (Calcium-sensing receptor, glycoprotein hormone receptors) which are much larger than the rest. Of those GPCRs exist about 3000 in humans, and most of the GPCRs are mostly very specific for one signal (i.e. agonist, e.g. a hormone, extracellular proteins, extracellular substances like ATP, neurotransmitters etc.) The important discovery Lefkowitz and Kobilka made is the following: The signal of those 3000 GPCRs is transmitted by a small family of proteins, the G-proteins, which are inside the cell linked to the inner side of the membrane. Those proteins exist of 3 subunits, alpha and beta-gamma. These proteins act like a self-deactivating switch. They are activated by a receptor and remain active for only some milliseconds after which they deactivate themselves and get ready for a new round of activation. There are only about 15 different G-proteins that are able to specifically transmit the signal from a GPCR and elicit a specific cellular response. Many GPCRs share the same G-proteins in their signalling, but induce very different effects. This is done by a very specific spatial and temporal control of the signalling processes by forming signalling microdomains where specific GPCRs, their G-proteins and downstream signalling molecules interacts with each other.
    To put it in a more technical analogy: you have 3000 buttons to press, but only 15 wires to transmit the analogue signal.
    I hope I could make things a bit more clear.

    Congratulations to the laureates!
    Best wishes
    1 post | registered
  4. Ray Stevens at Scripps is probably not in the most pleasant mood this morning.
    4933 posts | registered
  5. Fwiw, the other critical aspect of the GPCR signalling cascade is that it allows for a small external signal (e.g. a single activator molecule) to be greatly amplified within the cell in a process that is positive-feedback regulated to turn itself off.

    Incidentally, the GPCRs are also known as serpentine receptors as the protein chain, when diagrammed in 2D, 'snakes' back and forth through the cell membrane to give 7 transmembrane domains, which forms the core of the structure of the protein within the membrane. It is from this basic structural module that is commonly shared, the diversity of the internal and external activation and receptor domains can evolve.

    Last nugget of information for you - the vast majority of drugs you take act on GPCRs.
    380 posts | registered
  6. Anyone interested in understanding more about G proteins or any other topic related to cell signalling is highly advised to take a look at the web site titled Cell Signalling Biology. Its url is
    It is impressive even just as an example of the quality of scientific information that is becoming easily accessbile on the web.
    2101 posts | registered
  7. We just talked about that in university. It is amazing how fast new discoveries make their way into the curriculum.

    GPCR or even g-proteins in general are of huge interest for big pharma, as they are there way into regulating specific cell functions.
    Oh and to add to the informations. G-Proteins are the target for several pathogens as well. For example the cholera toxin keeps G-Proteins active in the cell of the intestinal tract, which in turn is a signal for the cell to include ion-channels into the membrane, thus changing the osmosis and therefore bringing you the usually associated symptoms.

    Kudos for the Nobel Prize Winners!
    346 posts | registered
  8. I am so proud to have worked with Brian Kobilka for 9 years, and here is what I think. He is a great scientist, and a great supervisor. He totally deserves this. He worked really hard on very fundamental questions in the domain of GPCRs, and never took shortcuts, never embellished the truth, and never published a paper he was not 100% behind. Here, we are so far away from all those reports of scientists gaming the system. He is incredibly honest and rigorous.

    He also does an incredible amount of work in the lab (hours a week, sometimes hours every day, in the lab, **not in his office**), working at the bench on many of the experimental details that eventually led to the successful crystallization of the beta2 adrenergic receptor. He definitely made the best of the postdocs and grad students that worked in the lab, but he was also a very strong link between each of them, and kept improving things over the years (in many labs, the techniques go away with the postdocs, not so here). The only flip side of this hard work is that most of the focus of the lab had switched to structural biology these past 10 years, so it was harder for the people still working on cell biology side. Such a focus was a bit of a professional risk, but that was the only way to get to these incredible structures.

    I don't know any of the other Nobel prize winners, but congrats on the committee for staying true to the spirit of science in their choice today.

    ADDENDUM: I should have made it clear that I don't work with Brian anymore (not for the past 3 years), and I have not much to do with any of the stuff he was rewarded for. And here is a great picture of him:
    162 posts | registered
  9. ↓ Moderation: spammer (show post)

    Nice fact. It is amazing how fast new discoveries are made.

    ⇒ Please read our policy on trolling. Questions about this moderation must be directed to our moderation team.

    2 posts | registered
  10. Great timing, I'm reading Blood Music right now so seeing the sort of thing that happens in the real world is pretty cool.
    8675 posts | registered
  11. I always enjoy gaining insight to my insides. Also, thank you to the other posters for filling out the details.
    106 posts | registered
  12. A wonderful series of discoveries and developments, true... but once again the Nobel in Chemistry ends up being awarded like they don't also have the Nobel in Medicine.

    - A Chemist
    339 posts | registered
  13. ChefJoe wrote:

    - A Chemist

    Derek Lowe at In the Pipeline has a nice commentary sorting through some of the same thinking. ... mistry.php Not trying to put down your point, just thought you'd enjoy reading it.
    4933 posts | registered
  14. Derek makes good points. Plenty of us chemists end up working in drug discovery rather than just synthesis.

    It's just that there's a "Nobel Prize for Chemistry" and a "Nobel Prize for Physiology and Medicine."

    If you were to ask which one I'd consider GPCRs to be more related to I'd pick the later, especially due to the word "physiology".
    Physiology (play /ˌfɪziˈɒlədʒi/) is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or Medicine
    339 posts | registered
  15. Just to nitpick:

    stelo_le wrote:
    Of those GPCRs exist about 3000 in humans

    800 different GPCRs in humans
    17 posts | registered
  16. Great comments.

    I realize it's short notice, but doesn't Ars have someone with a bio background writing for the science section? The article was really weak by Ars standards. I'd way rather wait an extra day or two for in-depth coverage of a *Nobel*.

    On the other hand, I got what I came for in the comments.
    379 posts | registered
  17. There is a video from periodic videos with some additional details - but true to their style still high level enough that you don't have to have a degree in molecular biology to understand it: ... e_2012.htm

    They seem to make a video with similar complexity of each winners achievement.
    190 posts | registered

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