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Biotech Science

Protein Researchers Win Nobel Prize In Chemistry 96

Posted by timothy from the moving-the-bits-around dept.
nucal writes "The 2003 Nobel Prize in Chemistry was awarded to Rod MacKinnon and Peter Agree for their work on proteins that form ion and water channels in cell membranes. In particular, solving the structure of potassium channels was a major achievement, since this was the first multispan transmembrane protein structure to be solved by X-ray crystallography. There is also structural information on aquaporins (water channels) as well."
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Protein Researchers Win Nobel Prize In Chemistry More

Protein Researchers Win Nobel Prize In Chemistry

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  • i think i speak for the majority of slashdotters when i say:

    what? what the hell are you talking about? whats a multispan transmembrane protein structure?

    i think we need someone to moderate the story posters.

    • In slashdot terms.. (Score:5, Informative)

      by k98sven ( 324383 ) on Wednesday October 08, 2003 @04:55PM (#7166000) Journal
      what? what the hell are you talking about? whats a multispan transmembrane protein structure?

      Ok, a protein is.. well a protein.. little things that do simple tasks in the body. Kind of like computer programs.

      The problem with proteins, is that even though we have the 'source code', (the sequence of amino acids forming the protein) we don't know what the things look like, since the chain can fold in a near-infinite number of ways. So it's important to figure out what the 3D-structure (positions of the amino acids) are.
      That way, we can get clues as to how the thing works.

      Now.. think of our cell.. it's like a computer, in the meaning that it contains lots of important data we want to keep safe. To stop anyone from getting in, we have a 'firewall'.. a cell membrane which stops intruders from getting in.
      Of course, a computer which is completly firewalled is not very useful, nor is a cell. It needs stuff from the outside.
      That's why we have these transmembrane proteins, which work as 'packet filters' and let molecules which are OK (like water, which is what Agre works with) in and out, but not suspicious, unwanted molecules.

      The potassium-ion channels are even cooler, because the 'operating system' (intracellular signalling) can turn them on and off when needed.

      Now a protein is a chain, right? So 'multispan' just means that the chain goes back and forth perpendicular to the membrane multiple times.

      • Re:In slashdot terms.. (Score:3, Funny)

        by Anonymous Coward
        The potassium-ion channels are even cooler, because the 'operating system' (intracellular signalling) can turn them on and off when needed.

        You know, the first think that came to my mind when you posted this was "imagine a Beowulf cluster of cells". Then I realized a Beowulf cluster of cells would be.. well, me I guess.

    • It's Mother Nature's own nanotech. The proteins are like Maxwell's Demon [wikipedia.org] but for water. Anything else is kept out and only H20 is passed in.

      Remember osmosis from high school biology? This is the mechanism that makes it work.

      The most remarkable thing is so much of this work used computational models of the proteins to understand how they work. This is one of those discoveries that become the basis for real cool SF science. We can now model, construct and manipulate structures on the atomic level.

      Now

      • Re:what (Score:2, Interesting)

        by k98sven ( 324383 )
        It's Mother Nature's own nanotech. The proteins are like Maxwell's Demon but for water. Anything else is kept out and only H2O is passed in.

        Well.. not really.. since they don't violate the second law of thermodynamics.

        We can now model, construct and manipulate structures on the atomic level.

        Take it easy.. we're not there yet by a far cry..
        If you want to model on the atomic level with any kind of accuracy.. you need to do quantum mechanics. The current methods (Nobel prize 1998 BTW) are reasonable for
    • This field of study involves protein that sit in cell membrane and control transport of substances (ions and water). Such proteins are involved in all sorts of important signalling functions in biology, but they have been very difficult to study because they sit in a cell membrane and are exposed on both the outside and the inside. This means that the outside parts has to be hydrophyilic (i.e. interact well with water) and the parts in the membrane has to be hydrophobic (i.e. kind of greasy). You can't even
      • Speaking as someone who spent 3 years trying (and failing) to do just that I can only agree with you - it is very hard - that's why people who have done it with particularly important systems have received Nobel Prizes (not all of them of course, these days (it *is* getting easier)).

        These days I write automation programs to help these guys out. Much less frustrating :).

    • Re:what (Score:4, Informative)

      by phch ( 398574 ) on Wednesday October 08, 2003 @05:51PM (#7166523)
      Proteins are biological polymers that are produced in living cells; they are composed of amino acids whose sequence is translated from DNA. The reason why the genome is of such great interest is that proteins provide the "molecular machinery" of the cell, to put things crudely; the genome provides a blueprint on how to assemble proteins, and the diversity of proteins gives rise to much of the cellular functionality essential for life.

      Determining the 3D structure of proteins is a very hard but essential part of learning how they work. Unfortunately, knowing the sequence of a protein (which you can derive from DNA) only gives hints about the 3D structure. There are a number of large computational projects such as Folding@Home [stanford.edu] and Blue Gene [ibm.com] that are devoted to predicting protein folding from a 1D sequence of amino acids to a 3D structure.

      X-ray crystallography is the traditional way of determining the structure of proteins; you basically analyze the diffraction pattern of X-rays from a crystal of the protein of interest.

      Now to your question: a multispan transmembrane protein is a protein that typically sits in the cell membrane that encloses the cell (alternatively, there are other internal membranes as well). Most of these proteins pass through the membrane several times, back and forth. These proteins are very important because they are involved in cell signalling and transport of substances into and out of the cell; ion channels are a prime example of transmembrane proteins. But transmembrane proteins are also notoriously difficult to study and crystallize because they do not solubilize without detergents, and are challenging to reconstitute in their native form.

      If you look in the Protein Data Bank [rcsb.org], there are lots of proteins that have been crystallized; but only a very small portion of them are transmembrane. This year's Nobel prize in part recognizes advances in studying the structure and function of these important proteins.
    • For a good presentation on the research go to http://www.rockefeller.edu/ [rockefeller.edu] and click on the interactive movie.

  • Drum Role Please (Score:3, Funny)

    by BrianGa ( 536442 ) on Wednesday October 08, 2003 @04:33PM (#7165934)
    And the Nobel Prize goes to...Folding@Home!
    • I remember a conversation with an undergrad friend of mine who went on to do Doctorate and Post-Doc work at John's Hopkins, working with the proteins that cell membranes use to connect to extracellular matrixes. I've lost touch with him in the last year (so Bob, if you read this, e-mail me), but from what I remember him saying about his work, I suspect he worked in this lab--though not on the project that was awarded the Nobel.

      However, as he explained it to this layman, it is much easier to determine the
      • I am willing to bet that it or other distributed computing projects are actually quite critical in the types of work represented by this Nobel prize.

        Nope. Refinement of structures often uses molecular dynamics, one of the classical simulation methods and also a (very slow) way of looking at protein folding. However, the software that does this is single-processor and actually doesn't require too much more power than a fast desktop. These structures were all at around 3-Angstrom resolution, and once you
        • I know of no important native biological structure solved with the aid of prior simulation; this is not to say that none exist, but you're grossly overestimating the importance of theoretical methods.

          Thanks for the clarification. As I indicated, the conversation was from the mid-90's and I was making the assumption of the applicability.

          I still find work like this fascinating on a number of levels. It's not work I could ever do, but unlike the kinds of work that often wins Nobels in Physics, I can usual
        • "These structures were all at around 3-Angstrom resolution, and once you're able to collect and properly phase X-ray data of that quality, the global structure is obvious."

          Having fitted a number of experimental 3A maps, I can unequivocally say that the global structure is far from obvious ;>. The phases are usually crap, you can't see sidechains, or tell which direction the chain is running. Anything that's not helix looks like a sausage with dysentary. Give me a nice 1A map of a small soluble enzyme a
          • Having fitted a number of experimental 3A maps, I can unequivocally say that the global structure is far from obvious

            Okay, "obvious" was overstated. I guess I meant it relative to protein-folding simulations, which are beyond useless for telling you the tertiary structure. 3A is still enough to indicate the overall fold, i.e. "global structure", even if sidechains are incomprehensible.

            CNS/CNX (the current versions of the molecular dynamics refinement program) works very well on multiprocessor systems,
            • Sorry, I shouldn't have included CNS on that reference-- I assumed that the parallel routines had worked their way back in (I remember Kay Diederichs saying she had some || routines on cnsbb last year). CNX definitly uses MP very well on linux machines. I'd rather use the free version as well, but Accelrys would sue me into the stone age if I tried ;>

              Anyway, traditional refinement/ manual fitting loops aren't amenable to distributed computing, but you could do something along the line of giving each cli
              • "Kay Diederichs saying she had some || routines on cnsbb last year"

                Damn typos.

                "Kay Diederichs saying he had some || routines on cnsbb last year"

                Sorry Kay ;>
      • I'd take that bet.

        Even with the most advanced, powerful folding techniques, I've yet to hear of a single case where a de novo computationally folded protein was close enough to fit the x-ray data in molecular replacement, which is probably the best test of whether the theoretical structure matches the observed structure-- a quick pub med search found nothing, either. Even NMR structures rarely work in molecular replacement (an NMR structure is basically a theoretical folding experiment driven by a massive

  • That was quick. (Score:5, Informative)

    by the gnat ( 153162 ) on Wednesday October 08, 2003 @04:41PM (#7165950)
    There was pretty much no doubt that MacKinnon would win it eventually - but it's a bit surprising that it came so soon, considering he's at the height of his career. He's only published four papers this year, but they're all Science or Nature (including one cover article). We can probably expect equally terrific work from him in the future.

    I interviewed with him earlier this year (I applied to Rockefeller largely because of his lab), and he's one of the most intensely brilliant people I've ever met. There are very few scientists who will master a completely different technique in the middle of their career, while working on the same area of research. Fewer still are able to dominate the field. When I took physiology in college, we read multiple articles which described hypotheses proved by a single figure in one of MacKinnon's papers.

    (There are actually an increasing number of membrane protein structures available, some of them quite large. However, ion channels are apparently especially difficult to study, and none were solved before MacKinnon started.)
    • He's only published four papers this year, .....When I took physiology in college, we read multiple articles which described hypotheses proved by a single figure in one of MacKinnon's papers.

      This is exactly why fewer papers published/year can be just as important if not more important than many publications/year. If your work tells the whole story and makes lucid arguments that clarify outstanding problems in science, you have contributed greatly while reducing the number of papers people have to read.
    • There are actually an increasing number of membrane protein structures available, some of them quite large. However, ion channels are apparently especially difficult to study, and none were solved before MacKinnon started.

      I'm not sure, if you consider cytochrome c oxidase as an ion channel protein, it's in a membrane.. it conducts hydrogen ions from one side to the other.. add that it 'pumps' them actively though.

      The CoX structure was determined back in 1994 (Iwata, et al, Nature, vol 376, 660), which I
      • Pumps are different. There is also a P-type ATPase, the calcium pump from muscle tissue, and the F1F0 ATPase, which pumps protons in the mitochondria. John Walker won the Nobel for the latter structures (although most of these were non-membrane). One of my former co-workers solved the cytochrome BC1 oxidase, also very large.

        I think (can't remember for sure) that one reason the channels are so difficult is that they're nowhere near as stable when you take them out of the membrane. Intuitively, this make
        • Membrane proteins are ridiculously hard to crystallize. In part, this is because they have large hydrophobic surfaces (for sticking into the membrane), so when you attempt to purify them they just form aggregates. It's a little hard to set crystallization trays 10-20 mg/ml when the protein isn't even soluble in cell lysate.
    • There are very few scientists who will master a completely different technique in the middle of their career, while working on the same area of research.

      What about not just changing fields, but inventing entire new ones [harvard.edu]? Stu Schreiber came in as a synthetic organic chemist and founded the field of chemical biology. I guess it is just a matter of time before he wins the prize.

      Also, anyone think it's strange that 2 chemists won the prize for medicine, and 2 doctors won the prize for chemistry? Chem
      • Chemistry What about not just changing fields, but inventing entire new ones?

        The study of membrane channel proteins -is- a new field, and these guys pioneered it.

        Chemistry != protein studies.

        If you mean that the subject of chemistry as a whole is not limited to the study of proteins, you are correct. If you mean the the study of enzyme mechanisms and structure is not part of chemistry, you need to get a clue.
      • "Also, anyone think it's strange that 2 chemists won the prize for medicine, and 2 doctors won the prize for chemistry? Chemistry != protein studies."

        Would you be surprised if a Computer Scientist won the prize for Math?
      • ...founded the field of chemical biology.

        You mean, uh, pharmacology? I guess it's easy to confuse novel grantwriting strategies with novel science, but it's hard to imagine that the Nobel folks will make that mistake...

        Off-topic and in a cold thread, but I'm always nervous that people will take this sort of thing seriously.
    • The structure of the potassium channel: Molecular basis of K+ conduction and selectivity Doyle DA, Cabral JM, Pfuetzner RA, Kuo AL, Gulbis JM, Cohen SL, Chait BT, MacKinnon R SCIENCE 280 (5360): 69-77 APR 3 1998

      Times Cited: 1588

      In general an article cited more than 400 times is considered a classic. Especially note how recently the article was published.

    • Cool. If Rockefeller admissions work the way I think they do, interviewing means that you had the opportunity to attend. Rockefeller is a posh place with excellent science. Are you working with ion channels now?

      What hypotheses do you mean? I guess voltage gating and inactivation, but I am curious.

      I imagine that ion channels are so difficult to study because they depend on lipid and water environments and they probably are a bit harder to produce in high concentrations. I know that he mostly looks at bacte
      • If Rockefeller admissions work the way I think they do, interviewing means that you had the opportunity to attend. Rockefeller is a posh place with excellent science. Are you working with ion channels now?

        I was already admitted when I visited. However, I didn't go there, for a variety of reasons; among others, there was no guarantee that I'd get to work in that lab, so it would have been foolish to go there solely because of one professor. I was mainly interested (and still am) in doing structural biol
    • Apparently, MacKinnon has worked on some of his x-ray crystallograpy in my father's synchrotron...
      He's scheduled to come in next thursday, I'll have to find out if he's going to make if, and if I can meet him.

  • WHOOSH (Score:3, Insightful)

    by Atario ( 673917 ) on Wednesday October 08, 2003 @04:43PM (#7165952) Homepage
    ...goes the sound of this news flying at Mach 1.3 over the heads of 99.99% of everyone reading it.

    Well, at least here on Slashdot I expect people (read: us geeks) will gape in awe instead of happily ignoring it.

    • Re:WHOOSH (Score:1, Flamebait)

      by Daniel Dvorkin ( 106857 )
      That's right. If you're too afraid of big words to read the article (which does a pretty good job of explaining the discovery in layman's terms) just make a whooshing noise. Apparently you take a perverse pride in your inability to understand anything more complex than plugging in your Xbox.

      No, it's not the post that pissed me off. It was the "Insightful" rating. Apparently, it's insightful to take pride in not understanding things. This is a particularly ironic attitude to find on Slashdot, since tec

      • Apparently you take a perverse pride in your inability to understand anything more complex than plugging in your Xbox.

        Ahem. Thank you for that, Mr. Jump On With All Four Feet Without RTFP.

        In case you hadn't noticed, your rant was exactly what I was saying:

        at least here on Slashdot I expect people (read: us geeks) will gape in awe instead of happily ignoring it.

        That's supposed to imply that we're interested in it, and don't take pride in not knowing.

        (Talk about whoosing over one's head...)

  • Off the beaten path (Score:5, Funny)

    by sssmashy ( 612587 ) on Wednesday October 08, 2003 @05:02PM (#7166027)

    To MacKinnon, the physician-turned-electrophysiologist-turned-crysta llographer, "the fun really begins once you have the structure."

    Physician-->Electrophysiologist--->Crystallograp her-->Nobel Laureate.

    Bricklayer-->Bodybuilder-->Movie Star-->Governor of California.

    There's definitely something to be said for nonlinear career choices...

    • Physician-->Electrophysiologist-->Crystallograp her-->Nobel Laureate.

      Bricklayer-->Bodybuilder-->Movie Star-->Governor of California

      Bricklayer-->Bodybuilder-->Movie Star-->Crystal? O, grope her-->Governor of California

      In the fullness of time, it had to happen! Slashdot word breaking to combat page widening produces a sort of poetry, and a commentary on current events!

  • New Headline... now in English! (Score:4, Informative)

    by Gestahl ( 64158 ) <gestahl@nOsPAM.gmail.com> on Wednesday October 08, 2003 @05:11PM (#7166107)
    Wow, way to make the headline inaccessible to anyone without a huge interest in biology... Basically MacKinnon solved the folding of extremely hard to study protiens in the cell membrane that allow ions into the cell. The cell membrane is non-polar (oily), while water is polar. These proteins exist so water, metal ions, etc. can get into the cell. What makes these protiens so hard to study is that when you try to remove them from the cell membrane to study them they turn inside out! The polar inside of the protein (which lets the polar stuff in) is attracted to the water, while the non-polar outside, normally attracted to the cell membrane, gets folded up to the inside (never knew a molecule could turn inside out before...).

    This kind of research has huge applications to medicine, since most drugs/poisons/anything not fatty have to enter the cell through these pores. I am wondering whether he used distributed or parallel protien folding simulations for some of his work... X-ray crystallography on globular protiens usually yields poor results (it is hard to get the X-rays to diffract to show the inner channel structure) compared to crystalline/regular protiens.

    • Re:New Headline... now in English! (Score:4, Informative)

      by cookie_cutter ( 533841 ) on Wednesday October 08, 2003 @05:50PM (#7166522)
      I am wondering whether he used distributed or parallel protien folding simulations for some of his work... X-ray crystallography on globular protiens usually yields poor results

      He did it through straight x-ray crystallography. See abstracts from the papers here [nih.gov] and here [nih.gov]. Find the structure here [rcsb.org].

    • I am wondering whether he used distributed or parallel protien folding simulations for some of his work...

      As the AC pointed out, none whatsoever. Almost nobody doing crystallography does, in fact. It continues to amaze me how many people think that simulations are going to replace experiment.

      X-ray crystallography on globular protiens usually yields poor results (it is hard to get the X-rays to diffract to show the inner channel structure) compared to crystalline/regular protiens.

      This is incorrect:
      • Quite right. People don't quite realise how hard it is to determine large structures at the level of theory required to replace experimental techniques. Never mind proteins; simulations of much smaller structures at a high level of precision is a very challenging task for today's computers.

        For one of my courses I have to optimize the geometry of a couple of molecules and carry out some further calculations on it. When I told him that my research is in porphyrins (large, sure, but much smaller than many/m
  • are important...
    i like proteins ;)

  • Dear Slashdot Readers,

    Due to a buffer overflow problem in my Outlook preview pane, someone was able to steal the source for SlashCode! Please note that they were only able to steal the source code that runs Slashdot, and not the actual content on Slashdot. Because of this unfortunate event, we have to shut down and re-code the network portions of SlashCode to avoid the inevitable trolling that might occur now that our source code is in the wild. The site will become progressively slower as we remove se

  • The first transmembrane protein structure was over 20 years ago, in 1982 (the photosynthetic reaction center, by Hartmut Michel). There have been 10-20 since, not lots, but NOT the first. Saying this is the first transmembrane protein structure is like saying SCO invented Unix. or something. The reason this is important is because McKinnon solved the first Potassium Channel membrane structure, which is a very important protein for channeling ions across the membrane (used in transmitting nervous signals)

  • Johann Deisenhofer was the first... (Score:1, Informative)

    by Anonymous Coward
    ... along with Hartmut Michel and Robert Huber to solve the crystal structure for a multi-pass transmembrane protein (bacteriorhodopsin). They, too, were awarded the Nobel Prize for their stunning work in 1988. MacKinnon's was for being the first to solve the structure of a protein that had remained elusive for so long and that had such critical biological relevance.
    • Hmmm. This *is* German science we're talking about here with something of an emphasis of team playing ;-). My understanding of the situation was that Michel did most of the work (and had the insight about using a long chain alcohol molecule to enable crystal growth), Huber provided the X-ray machine and computational facilties (important, but nothing that couldn't be substituted by any one of dozens of other PX labs - he was just in the same building at the time) and Deisenhofer was in simply charge of th

  • Hmmm... (Score:3, Funny)

    by disntrstd ( 705189 ) on Wednesday October 08, 2003 @06:04PM (#7166641)
    Isn't "protein research" just a fancy Chemist term for pleasuring yourself in the lab?
  • This might be slightly off topic but what is wrong with chemistry today? Enrollment in the chemistry major has been declining for quite a bit I believe. Is it that they do not get the toys of the physicist or the presitge of the biologist?
    • Part of it, I suspect, is that outside of biological chemistry and a few other select fields, there's really not all that much money for research out there. If you're not into organic chemistry of some sort, it's rough.
      • Thats just simply not true! Well, at least not in the UK. There is funding available to a whole variety of chemistry disciplines.....you (as a researcher) just has to prove to the funding bodies that its worthwhile.
        • That there is funding available is immaterial when it's enough to fund maybe ten projects and it's divided among 600-700 or more. Mind, I am speaking of the US funding situation, I really can't say anything about the UK on that issue.

          And I won't go into the joys of academic politics in which one is more rewarded for getting more funding than one is for teaching OR doing research.

  • What to do with the $1.3 million? (Score:3, Funny)

    by cpopin ( 671433 ) on Wednesday October 08, 2003 @06:52PM (#7167036) Homepage
    When asked what to do with the $1.3 million awarded, he answered (on NPR), "Since they couldn't get a hold of me and I found out second hand, I decided to buy a cell phone."

  • Cn3D see it for yourself (Score:3, Informative)

    by paughsw ( 620959 ) on Wednesday October 08, 2003 @07:18PM (#7167228)
    Get Cn3D here [nih.gov] and then look at the potassium channel here [nih.gov] in 3D.

  • hot-rod (Score:1, Funny)

    by Anonymous Coward
    i'm currently a student at rockefeller - and am rotating in rod's lab; you may not be surprised but a large majority of the lab are /.ers. and you know what working in the lab of a nobel prize winner makes us? thats right. nothing. cheers!
  • MacKinnon and his co-workers are responsible for determining the crystal structure of the potassium ion channel protein, of fundamental importance to many biological processes, include nerve impulse transduction. Pictures of the tetrametric (four identical proteins complexed together) channel are available in the Science paper [sciencemag.org], or at the protein data bank [rcsb.org]. If you have the appropriate viewer (such as Chime [mdlchime.com] or RasMol [bernstein-plus-sons.com]) you can view the structure in 3D [rcsb.org]!

    -c

  • Nobel winner to fight US terror rules (Score:4, Interesting)

    by pararox ( 706523 ) on Wednesday October 08, 2003 @09:01PM (#7167868)
    Perhaps the most interesting outcome of this years Nobel prize winners, is that:

    "One of the two Americans who won yesterday's Nobel prize for chemistry said he might use some of his award money to help defend academic freedoms against restrictions imposed on scientists as part of the US war on terrorism." (news.telegraph)

    Hurrah for those who still aspire to pure learning! The full article may be viewed here, if you're interested:

    http://www.telegraph.co.uk/news/main.jhtml?xml=/ne ws/2003/10/09/wnobel09.xml&sSheet=/news/2003/10/09 /ixworld.html [telegraph.co.uk]

    Regards,
    -pararox-

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