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Analytical Chemistry

GPCRs Are As Crazy As You Thought

That’s my take-away from this paper, which takes a deep look at a reconstituted beta-adrenergic receptor via fluorine NMR. There are at least four distinct states (two inactive ones, the active one, and an intermediate), and the relationships between them are different with every type of ligand that comes in. Even the ones that look similar turn out to have very different thermodynamics on their way to the active state. If you’re into receptor signaling, you’ll want to read this one closely – and if you’re not, or not up for it, just take away the idea that the landscape is not a simple one. As you’d probably already guessed.
Note: this is a multi-institution list of authors, but it did catch my eye that David Shaw of Wall Street’s D. E. Shaw does make an appearance. Good to see him keeping his hand in!

6 comments on “GPCRs Are As Crazy As You Thought”

  1. luysii says:

    It is totally insane to think that a protein such as a GPCR with over 400 amino acids has just one or two conformations. What I find remarkable is that it has so few. http://luysii.wordpress.com/2010/08/04/why-should-a-protein-have-just-one-shape-or-any-shape-for-that-matter/

  2. Anonymous says:

    David Shaw is actually on quite a few high-profile papers these days – see, for example:
    doi: 10.1073/pnas.1218321110 (PNAS 2013)
    doi: 10.1016/j.cell.2012.12.032 (Cell 2013)
    doi: 10.1038/nature11701 (Nature 2012)
    doi: 10.1126/science.1216533 (Science 2012)

  3. modeller says:

    David Shaw isn’t really “of Wall Street” anymore – his operational efforts have been primarily at DE Shaw Research for a while now, churning out Science papers with Anton the MD machine. Very cool work.

  4. barry says:

    that GPCRs have relatively few accessible conformations is the least of the mystery. That the human genome preserves almost 800 of them remains to be explained. Some are important drug targets. Many of the rest seem to be olfactory. Obviously it’s a neat piece of nanotechnology that has been used again and again biologically.

  5. anonymous says:

    Folks from DE Shaw seem to have purely honorary authorship on this paper, seeing as it is fluorine NMR (done by Prosser’s lab on samples most likely made in Kobilka’s lab). There is no MD in the paper or any other obvious DE shaw contribution. Perhaps they have contributed “useful discussions” or some such thing that we, the scientists, usually claim when pressed to explain this mild form of dishonesty.

  6. A. Postdoc says:

    Shaw is a crackpot billionaire who everybody sucks up to get some of his money. None of his papers/contributions to science are any better than some first year grad students JCIM paper, but because he’s a billionaire he gets to publish in Cell, Nature and Science. A better example of a truly sick and stupid system couldn’t be designed.

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