Pharyngula

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The Harvard multimedia team that put together that pretty video of the Inner Life of the Cell has a whole collection of videos online (including Inner Life with a good narration.) Go watch the one titled F1-F0 ATPase; it’s a beautiful example of a highly efficient molecular motor, and it’s the kind of thing the creationists go ga-ga over. It’s complex, and it does the same rotary motion that the bacterial flagellum does; it has a little turbine in the membrane, a stream of protons drives rotation of an axle, and the movement of that axle drives conformation changes in the surrounding protein that promote the synthesis of ATP. It’s a molecular machine all right. Makes a fellow wonder if possibly it’s “irreducible”, doesn’t it?

Well, it’s not. It can be broken down further and it still retain that rotary motion.

First, let’s look at some stills from the Harvard movie. This is the overall structure of the complex; the blue and green parts are the α and β subunits, which are responsible for the actual ATPase activity.

i-029ded0cbcb4f893ca16c65e71ac2b73-f1f0.jpg

In this next image, the α and β subunits have been removed to expose the γ subunit, in orange, which is the axle of the whole complex. Put α and β together with γ and some ATP, and the α and β break down the phosphates and set γ to spinning. This can even be visualized; anchor the α and β proteins to a glass slide, attach some 40-nm gold beads to the γ subunit so that you’ve got something large enough to see, and you can make movies of the motion, study rotational kinetics, etc. Furuike et al. have described exactly that in a recent issue of Science.

i-f26e8b4fc7cd7376e7e351e3fd9f1ef7-stalk.jpg

The researchers took another step, though, one that was intended to study further details of the molecular interactions involved in ATPase activity, but which also tells us something about the evolution of this motor and undercuts creationist claims of “irreducible complexity”. They created modified versions of the proteins; in particular, they made various truncated forms of the γ subunit, the axle, that eliminated the axle structure. A wheel without an axle? What good is that?

This is an illustration of their modified γ proteins. It’s upside down relative to the Harvard movie, unfortunately, but the color scheme is the same — the axle is red and orange, while α and β are blue and green. In D is an axle with just the tip deleted; in F, the whole thing is gone, and we just have the base of the γ protein bouncing about on top of the α and β subunits.

i-6ed438f6453c915ec131a809acce6f41-trunc_axle.jpg
An atomic structure of MF1. (D to F) Structures of γ-ΔN4C25 (C and D) and γ-ΔN22C43 (E and F). For γ-ΔN4C25, γ-Met-4 is represented by γ-Lys-4, excluding the ε-amino group to mimic Met. For γ-ΔN22C43, γ-Met-22 is represented by γ-Ser-22. Atoms of γ that are within 0.5 nm from an atom of α or ? are shown in gold and brown (there were none on the C-terminal helix of γ-ΔN22C43). Black circles in (F) show approximate locations of biotinylated cysteines.

Now the surprise: these axle-less mutants still spin! Even the stumpy one that has no axle at all. And the rotation is in the correct direction. The authors note that this is a rather substantial difference from man-made machines.

Most manmade rotary machines rely on a rigid axle held by a static bearing: thanks to the constraint exerted by the bearing, almost any force acting on the axle is converted to a torque through a lever action. Nature seems to have adopted this simple principle for the bacterial flagellar motor and the proton-driven Fo motor of the ATP synthase: Their rotor axis is held stationary by stator bearings, and thus force from one driving unit, acting on only one point on the rotor, suffices to produce torque. For the short γ mutants here, however, the concept of a rigid axle in a static bearing no longer applies. Yet the mutants do rotate.

What was also observed, though, is that the efficiency is greatly reduced: rotation is more halting, and the likelihood of the γ subunit actually binding to the α/β complex is much lower. The more complete the axle, the more reliable the rotation became. This is obviously what we’d expect from evolution: that a molecular machine would not be an all-or-nothing affair, but that incremental variations would produce incremental changes in efficiency.


Furuike S, Hossain MD, Maki Y, Adachi K, Suzuki T, Kohori A, Itoh H, Yoshida M, Kinosita K Jr. (2008) Axle-less F1-ATPase rotates in the correct direction. Science 319(5865):955-8.

Comments

  1. #1 Bruce
    March 20, 2008

    What a great little movie. I thought I heard them say that the unequal forces of protons through the membrane (at the portion of the molecule that was “blanked out”) act to spin this entire molecular unit; is that right? If so, that is way cool! Proton power!

  2. #2 Clan:Rewired
    March 20, 2008

    “The authors note that this is a rather substantial difference from man-made machines.”

    Well obviously! God made these motors!

    3… 2… 1… let the cursing begin…

  3. #3 Richard Eis
    March 20, 2008

    Because of all the fuss I had always assumed the flagellum motors and their like were, shall we say, more designed looking.

    Well, to the casual observer (me) that’s a blob.

    I would have a hard time standing up and explaining how this erm…blob was “designed” i can tell you…
    In fact i could actually believe that the thing had randomly accumulated, never mind evolution.

  4. #4 Mrs Tilton
    March 20, 2008

    DI @3,

    It’s a strawman attack on intelligent design

    ID creationism doesn’t need attacking; it fails quite well enough all by itself.

    Now get back in your oubliette.

  5. #5 MartinM
    March 20, 2008

    This molecular motor is unevolvable, not because you can’t take it apart without it losing it’s function, it’s unevolvable because you can’t put it together in the first place using only random, non-directed, accidental occurrences. The selection of the parts, the configuration in which they’re aligned, the assembly into one unit all require intelligent decisions at every step of the way.

    And your evidence for this is…?

  6. #6 Richard Eis
    March 20, 2008

    Dungeon Inhabitant – Argument from ignorance.

    Science is haaaaard…I’m too stupid to work it out so i’m going to give up and say my God did it.

  7. #7 Richard Eis
    March 20, 2008

    Cite one piece of empirical evidence, either observational or experimental that establishes an unequivocal nexus between the trivial effects of mutation and natural selection and the emergence over time of the highly organized structures, processes and systems found in living organisms.

    Erm…the fossil record

  8. #8 James W
    March 20, 2008

    “The argument that this molecular motor is not “irreduciby complex” is a red herring. It’s a strawman attack on intelligent design.”

    DL – this is an absolutely outrageous statement. Michael Behe has made a career out of making this very claim over and over again – it’s the very basis of the mousetrap argument: that taking away a component of the system renders it non-functional, rather than gradual chnages making gradual improvements (which is what the evolution of complex fuunctions requires (iiuc).

    “The important point is that the adaptation of means to ends, the adaptation of structure and process to function requires insight. This molecular motor is unevolvable, not because you can’t take it apart without it losing it’s function, it’s unevolvable because you can’t put it together in the first place using only random, non-directed, accidental occurrences. ”

    Really? I appreciate that you ID types make this claim on a regular basis, but has anyone actually demonstrated it? Both Irreducible Complexity and it’s evil step-twin Specified Complexity (/CSI) are nothing more than arguments thhat assume the conclusion. Noone has managed to demonstrate that complexity can’t evolve from an undirected process – noone. Go on – try and find someone.

    And before you say that “None has proved that it CAN” – (and I’m not an evolutionary biologist and couldn’t say), bear in mind that this is nothing but shifting the goal posts. You made a positive statement, and I’m asking you to back it up.

    I’ll be waiting.

  9. #9 mike fox
    March 20, 2008

    The model atpase looks like a tree with a spinning trunk.

  10. #10 David
    March 20, 2008

    What happened to “Dungeon Inhabitants” comments? I thought they were kind of silly, but not deserving of almost immediate deletion. Especially considering that a couple of other comments reference his.

  11. #11 Richard Eis
    March 20, 2008

    Not directly I know, but since we both know what game he is playing…I thought i’d play too rather than getting all huffy.

    There are however mutations within populations, and since populations do change over time as noted in the fossil records (all those intermediate species) I really don’t see why that can’t be infered from what we know. Especially once you throw in Genetics.

  12. #12 sublunary
    March 20, 2008

    There is NOTHING in the fossil record that supports mutation and natural selection as the mechanism of evolution

    Ok, my turn to try (though why I’m bothering I’m not sure), so how about gene research that looks at how genes and their functions in one species relate to those in distantly related species.

    Quickest example is PZ’s write-up yesterday regarding the vestigial yolk sack in human embryos and the genes that would be involved in making yolk if we still did that. Here

  13. #13 MartinM
    March 20, 2008

    What happened to “Dungeon Inhabitants” comments?

    The name indicates that he’s a previously banned poster, so not really surprising that he’s not welcome.

  14. #14 Mike Haubrich, FCD
    March 20, 2008

    You have a point, DungeonInhabitant. I can’t explaim how the molecules of liquid water conform to the shape of a lake, a river, a pond or a puddle either. How did they ever randomly “choose” that shape? How does the gas in a rubber balloon “know” the shape of the balloon to fill it out? How does hemoglobin “know” that the iron is supposed to bind with oxygen? How do my shoes “know” to stop going down when they meet the floor. If they go too far, then they will go into the floor and I will get stuck. If they don’t go far enough, then I will gain no traction. It must be a Designer that does all of these things. Because we all know that biology has nothing to do with physics and chemistry, don’t we? It’s a completely separate thing, something which depends on magic. Physics and chemistry don’t.

    PZ is just making stuff up because he is an atheist and wants to have a good excuse to eat children and puppies.

  15. #15 Richard Eis
    March 20, 2008

    I have clearly demonstrated that organization cannot arise from random processes.

    If you have, i ain’t seen it…and that would be a bit hard because you would be proving a negative.
    and oy they’re my goal posts…stop running away and give them back.

  16. #16 Mike Haubrich, FCD
    March 20, 2008

    Abu, you can’t clearly demonstrate something which is not true unless you make stuff up.

    Also, randomness is only a single process and not the entirety of evolution.

    Will that fall on deaf ears?

  17. #17 Tulse
    March 20, 2008

    Simply, he can’t defend himself against my criticism, so he runs away

    What’s the emoticon for “eyeroll”?

  18. #18 Natasha Yar-Routh
    March 20, 2008

    “The important point is that the adaptation of means to ends, the adaptation of structure and process to function requires insight. This molecular motor is unevolvable, not because you can’t take it apart without it losing it’s function, it’s unevolvable because you can’t put it together in the first place using only random, non-directed, accidental occurrences. ”

    ARRGGGHHHH!!! It may be random but it IS NOT NON-DIRECTED. The whole point of natural selection is there is SELECTION, the motor even without an axle gives a competitive advantage. This means the organisms that have that advantage become the predominate part of the population.

    The creationists seem totally unable to grasp the basic principals of Darwin’s theory, they are either stupid or willfully ignorant, maybe both. Evey time we beat down one of their arguments they either go Nu Hu or move the goal posts.

  19. #19 Mike from Ottawa
    March 20, 2008

    A rotary motor without an axle. That’s literally wonderful stuff.

    I derive a certain schadenfreude knowing that the creationists like the ones appearing above deprive themselves of the enjoyment of the wonder of it. And it’s rendered guilt-free by the knowledge that folk like Abu inflict it on themselves by choosing ignorance and dishonesty.

  20. #20 Rey Fox
    March 20, 2008

    So it doesn’t behave like a machine that wae know was designed when we knock out a part. But it still looks designed, according to my handy Dembski Design Detector 3000?.

  21. #21 Richard Eis
    March 20, 2008

    Well, they can’t change their minds, but they don’t have anything new to say…so that only leaves one option to avoid cognitive dissonance.

    Actually completely off topic, but can anyone tell me the average variation in blowhole location (from the optimal) seen in the humpback whale species.
    I know it’s a rather vague question but basically I want to know if the blow hole location is directly related to the size of the whale or if it can appear in a sub-optimal location within the modern species regardless of size.

  22. #22 sublunary
    March 20, 2008

    Richard, in the event that no one here knows the answer to your question (I certainly don’t). I’d try Ask a Biologist. They could probably help, and they seem to be looking for more traffic (and more questions).

  23. #23 Elf M. Sternberg
    March 20, 2008

    It’s certainly a valuable video to compete with the other one, which looks far too much like the inside of your standard electric motor. This looks more… messy. Biological. What’s really going on, not some hand-drawn animation.

    Unfortunately, it’s also complexifying. The cdesign propononentists will dismiss it.

  24. #24 Jud
    March 20, 2008

    Mike (#16):

    I can’t explaim how the molecules of liquid water conform to the shape of a lake, a river, a pond or a puddle either.

    Exactly. And those shapes are incredibly complex, and it is as unlikely as a tornado assembling a 747 that those same shapes would appear if we “ran the movie over again.”

    Hmm, I think I just proved the existence – nay, the necessity – of Slartibartfast. See http://hitchhikers.wikia.com/wiki/Slartibartfast .

    Also, your comments about how hemoglobin “knows” it’s supposed to bind with oxygen remind me of this old joke:

    Three fellows are arguing over the question of what is the greatest invention of all time. One votes for the wheel, the second for fire, the third for the Thermos. The other two immediately ask why. The third fellow says:

    “You put something hot in it, it stays hot, right?”

    “Yep.”

    “And you put in something cold, it stays cold.”

    “Yep.”

    “So how does it know?”

  25. #25 SteveM
    March 20, 2008

    I have clearly demonstrated that orhanization cannot arise from random processes:

    Didn’t some one prove (rigorously) that random processes inevitably produce apparent patterns? So I find it hard to believe that you have proved the opposite.

  26. #26 Richard Eis
    March 20, 2008

    Thanks Sublunary, I had completely forgotten about that site. Silly me.

    quick…to the batmobile.

  27. #27 sparc
    March 20, 2008

    This is obviously what we’d expect from evolution: that a molecular machine would not be an all-or-nothing affair, but that incremental variations would produce incremental changes in efficiency.

    Too true. Let’s see if UD’s own DaveScot will change his calculation of ATP synthase’s CSI in the recent human/chimp thread.

  28. #28 Brian
    March 20, 2008

    Dammit. I went to college too early. If my organic chemistry teacher had had videos like these, I’d have been all over that.

  29. #29 trimtab
    March 20, 2008

    “… stream of protons…”

    Protons!? Hmmm. A stream of electrons, sure, but protons? Holly cold-fusion, Batman!

  30. #30 Josh
    March 20, 2008

    It looks like they added a little brownian motion to the animation. It does help the little organic machine look more organic and less machine. It’s probably less likely this animation will be stolen by a creationist/IDiot because it doesn’t show the clockwork biology they imagine inside cells. Perhaps the animators heard your criticisms of the earlier animations PZ.

  31. #31 mattmc
    March 20, 2008

    Good stuff PZ….

    “Protons!? Hmmm. A stream of electrons, sure, but protons? Holly cold-fusion, Batman!”

    Trimtab:
    Proton = H+ ion

  32. #32 PZ Myers
    March 20, 2008

    In case you’re wondering about the missing comments: they’re all from the obsessed kook, Charlie Wagner, who has been banned with extreme prejudice, and will not be allowed to post here ever again. He is constantly morphing his name now, but his style of obtuse arrogance is instantly recognizable and deleted on sight.

  33. #33 Dan
    March 20, 2008

    Cite one piece of empirical evidence, either observational or experimental[,] that establishes an unequivocal nexus between the trivial effects of mutation and natural selection and the emergence over time of the highly organized structures, processes[,] and systems found in living organisms.

    Start with a moderate length: say 1 meter. Add to it 0.1 millimeter. A trivial effect. You couldn’t tell by looking at it, only through detailed measurements. There’s almost no difference!

    Add to that 0.1 millimeter. Add to that 0.1 millimeter. Do it once a day. As time goes on the effect of adding 0.1 millimeter becomes even *less* pronounced, because it’s fractionally smaller.

    Repeat for a brief time — say one million years. The length is now 36,500 meters! You will notice “an unequivocal link between the trivial effects of adding 0.1 millimeter and the emergence over time of a highly long structure”.

    Now, for you, two questions:

    (1) Since this happens for length, why do you think it can’t happen for organization?

    (2) What does “nexus” mean?

  34. #34 CrypticLife
    March 20, 2008

    “[PZ] wants to have a good excuse to eat children and puppies.”

    Well — it does end in “pies”, and PZ has said he wants his pie quite forcefully. He’d actually prefer it floating over his keyboard for easy access. I think this statement may not be too far off the mark.

  35. #35 Dan
    March 20, 2008

    I have clearly demonstrated that organization cannot arise from random processes.

    You’re not the first to make this observation.

    In 1985, writing in Origin of Species, Charles Darwin says that “mere chance … alone would never account for so habitual and large an amount of difference as that between varieties of the same species and species of the same genus.”

    Richard Dawkins makes the same point in his book The Blind Watchmaker, where he concludes a long and delightful explanation by writing that: “This belief, that Darwinian evolution is ‘random’, is not merely false. It is the exact opposite of the truth. Chance is a minor ingredient in the Darwinian recipe, but the most important ingredient is cumulative selection which is quintessentially non-random.”

    Why do so many people share the misconception that evolution is a random process, even after distinguished and literate scientists from Darwin to Dawkins have labored so hard to dispel it?

    Please, Mr. Eis, let us know!

  36. #36 sparc
    March 20, 2008

    In 1985, writing in Origin of Species, Charles Darwin says

    103 years after he passed away?

  37. #37 Mrs Tilton
    March 20, 2008

    Dan @35,

    Richard Eis isn’t the ID creationist troll here, he was just piling on like the rest of us. You’re confused because (i) PZ deleted the troll’s comments, the troll in question having long ago been banned, and (ii) Eis didn’t set apart the bits he was quoting from the troll with italics or blockquotes or what have you. Those two factors together combined to make you think (quite reasonably) that Eis was saying the things the troll had actually said.

  38. #38 John
    March 20, 2008

    Dan wrote:
    “Why do so many people share the misconception that evolution is a random process, even after distinguished and literate scientists from Darwin to Dawkins have labored so hard to dispel it?”

    Dan, I disagree with the way you’re framing that question. A better way to phrase it is:

    “Why, when we patiently explain to every creationist/IDer that evolution is not random, do they continue to use this false premise? While the first instance may be due to ignorance, later instances can only be attributed to dishonesty–an explicit renouncing of the Ninth Commandment. How could a desire to use a dishonest, straw-man argument possibly be more important than obeying God’s Commandments? Why don’t the leaders of creationist organizations explain to the public that evolution is not random?”

  39. #39 Cory Albrecht
    March 20, 2008

    That video is cool.

    Is the F1-F0 ATPase the same mechanism that proton-pump inhibitor drugs (used to reduce gastric acid prodction) as mention in < http://en.wikipedia.org/wiki/Proton_pump_inhibitor>?

  40. #40 tcb
    March 20, 2008

    Great post title, PZed. (But I’m easily entertained.)

  41. #41 MandyDax
    March 20, 2008

    Tulse (#17):

    What’s the emoticon for “eyeroll”?

    I use e_e

  42. #42 Jim Batle
    March 20, 2008

    After watching the video, I think this exclamation is off the mark: “Now the surprise: these axle-less mutants still spin!”

    The video makes it very clear that the rotation is driven by the “F0″ structure. The axle that extends into the “F1″ structure is used to drive the conformational changes that are required for ATP synthesis. It seems that F1 could be outright gone and F0 would still spin. F1, in fact, is a drag on the axle. F1 does serve a purpose, perhaps, of preventing the F0 structure from floating away — it pins the axle in place.

    The real evolutionary question would be: with the stubby F0 axle, does the F1 structure still produce ATP? If it doesn’t, then it argues against incrementalism.

  43. #43 Ted Powell
    March 20, 2008

    Is it possible, when deleting a comment, to replace it with, e.g., (DELETED) so as not to skew the comment numbering?

  44. #44 ngong
    March 20, 2008

    The real evolutionary question would be: with the stubby F0 axle, does the F1 structure still produce ATP? If it doesn’t, then it argues against incrementalism.

    Hardly. I don’t think anybody is claiming to reproduce some sort of evolutionary pathway here. Even if that true, you’d have to test a myriad of stubby F0 units (as nature is able to), not just a handful.

  45. #45 Jim Battle
    March 21, 2008

    ngong — I’m speaking through a aperture not normally associated with vocalization; I’m just a EE/programmer type, so please indulge my ignorant persistence.

    The underlying concept of irreducible complexity is that things are so finely tuned and so interdependent, that it would not be possible for such a structure to be built incrementally, as there would be no adaptive advantage until the totality (more or less) was in place. PZ said,

    “Makes a fellow wonder if possibly it’s “irreducible”, doesn’t it? Well, it’s not. It can be broken down further and it still retain that rotary motion.”

    The thing that seemed odd to me was that there was emphasis that even if the load on the motor was broken, the motor still managed to turn. That seems hardly surprising at all.

    A portion of the original article was quoted saying that man-man motors have an axle which is supported on both ends, yet here is a biological motor that works even if one end is broken off. The analogy is lost on me, as the relative forces that apply at the macro scale are very different at the microscopic scale. I could easily imagine that even with one side of the axle broken off, the stiffness of the shaft on the still intact side and the electrostatic forces of the side that interacts with the F1 structure is sufficient to preserve some function of the original unit.

    It would also surprise me if one couldn’t also create such a motor on the macro scale, one where the axle is supported on a single side. Nobody does it because it results in inferior performance, but F0-F1 ATPase motor above suffers the same consequence.

    In another point, the video states that this motor operates at nearly 100% efficiency. That is cool, but keep in mind that man-made electric motors that get to operate at a constant load can achieve north of 95% efficiency.

    Still, all in all, it was a good read, and seeing the video with a bit of the effects of real world probabilistic operation (brownian motion and such) makes things much more compelling.

  46. #46 Jud
    March 21, 2008

    Jim Battle wrote:

    I could easily imagine that even with one side of the axle broken off, the stiffness of the shaft on the still intact side and the electrostatic forces of the side that interacts with the F1 structure is sufficient to preserve some function of the original unit.

    PZ wrote in the original post:

    Now the surprise: these axle-less mutants still spin! Even the stumpy one that has no axle at all.

    Not “one side broken off” and one “still intact side.” No axle at all. OK, Jim, how easy is it for you to imagine preservation of function of “the original” now? (And what causes you to designate the more complex rather than the less complex structure as “the original”?)

  47. #47 VK
    August 26, 2008

    The original website appears to have been completely reorganized, and the movie referred to here is not listed at all. Any idea where it can be found now? Thanks!

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