June 16, 2008 | David F. Coppedge

Magic Box in the Cell Baffles the Experts

Put a string of amino acids into this magic box, and it comes out all precisely folded into a protein.  How does it do it?  A molecular machine described by Science Daily has scientists baffled.  Ironically, its name is TRiC.
    TRiC is a chaperonin, a member of a class of molecular machines that “chaperone” or guide polypeptides emerging from the ribosome (the translation machine, 02/21/2007) into their final folded shape.  The shape of a protein is essential to its function.  Most polypeptides find their native fold without help, but about 10% need a chaperonin shelter, like a private dressing room (05/05/2003) to get in shape.
    The article shows that TRiC looks like a barrel-shaped box with two lids.  Each lid opens and closes like the iris of a camera.  Scientists can’t see what goes on inside when the box is closed.  The press release explains,

TRiC, like all chaperonins, consists of a double-ringed structure that gives it a barrel shape.  One ring opens to admit the raw protein into the inner recesses of the folding machine, then closes tightly while, inside the chaperonin “black box,” the mysteries of molecular origami unfold—or, more correctly, fold.  Upon completion of the folding, the ring at the other end opens up to push out the finished product.
    “It is really like a nanomachine.  It closes off, the protein is trapped inside and something—we don’t understand what—happens inside this chamber, and the protein comes out folded,” Frydman said.  “It is a very complex mechanism.”

What’s remarkable about this cellular magic trick is that there are many more possible incorrect folds than the right one.  How this machine can fold each protein correctly, like solving a Rubik’s Cube in the dark without hands, is one of those mysteries of life science is trying to unlock.  It’s not just the shape of the box that matters.  The two iris-like lids have to open at the right time, and keep the protein inside the right amount of time, or it doesn’t work and the product comes out misfolded.
    Judith Frydman at Stanford discovered TRiC in 1992 and has been trying to figure it out ever since.  Co-director of the Center for Protein Folding Machinery, Frydman describes TRiC as a “two-stroke motor” wherein the opening of one end is linked to the closing of the other end.  “What has been so intriguing is that everything is connected,“ she said.  “This is a very large machine and every part of the machine is communicating with the other parts.”At first her team thought the machine opened like the flaps on a cardboard box, but then they discovered the iris-shutter mechanism.  She thinks the twisting of the lid transfers rotational motion to the interior and this helps the folding process, but so far the secret is still hidden inside.
    If Frydman and her team figure out the TRiC, new medical advances may be forthcoming.  She said, “If one could understand what the environment in there looks like, what this machine does, what the cell does to fold its proteins, then we could begin to design ways to fold proteins for therapeutic purposes.”  This implies design following design.  In fact, no mention of evolution or natural selection was made in the press release, originally published by the Stanford University news service.  The chaperonin is called a machine eight times in the brief article.

This science project needs evolutionary theory like a fly needs a swatter.  Tell us, Charlie, how the protein machinery that codes, transcribes, translates and folds proteins originated without the machinery to do it.  We want scientific facts, not stories.
    Magic tricks intrigue us, not because we think real magic is happening, but because we want to know how the trick is done.  TRiC is inspiring Frydman and her colleagues to reverse-engineer the implicit design of this complex black box and put their findings to practical use for improving human health and well being.  Isn’t that what science is all about?
    Surely no one from Darwin’s day through the 1950s could have imagined that the secrets of life would depend on complex, precision machinery, with moving parts, made out of molecules, manufactured to spec from coded instructions.  Enough reports like this one, and Darwinism itself will be interred in a black box: coffin-shaped and nailed shut, so the folding of rigor mortis inside won’t gross anyone out.

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