Even Molecules Need Chaperones
by Matt J. Carlson
Using a technique called x-ray crystallography, molecular biologists have gained a glimpse of one of the small-scale wonders of the universe: moelcules "shepherding" other molecules. In this case, the shepherd molecules, appropriately dubbed chaperonins, prevent newly-formed protein molecules from clumping into disorganized, useless globs.(1)
Proteins are strings of amino acids. Some parts of the strings are greasy and some are nongreasy, or "polar." When proteins are in water, as in our bodies, the greasy parts clump together to form the inside layer of the folded proteins, and the polar parts, which like to be next to water, form the outside layer. This clumping, or folding, process is crucial. Proteins can only do their job if they take on the right configuration. They don't work in their stretched out, string-like form.
In many cases, a protein's sequence of greasy bits and polar bits along the string is enough to enable the protein to fold into its useful shape, but sometimes a protein gets stuck, or misfolds. Here's where the chaperonins come in: they protect against misfolds.
Recent work at Yale University has allowed researchers a close-up view of a particular chaperonin doing its intricate job.(2,3) This chaperonin is a large molecule consisting of two rings of seven copies (each) of protein GroEL. These fourteen GroEL proteins form something that looks like two stacked doughnuts with a bit of waxed paper stuck between them. The two doughnut holes, or pockets within the doughnuts, have greasy area that attract misfolded proteins. Once a misfolded protein is enticed into the GroEl pocket, another part of the chaperonin, a structure made of seven GroES proteins, caps the hole.
This action by the GroES7 forces the GroEL14 to twist, producing two important changes in the pocket containing the misfolded protein. First, the pocket stretches as it twists, thus stretching out the clumpy protein as it clings to the greasy areas. Second, the twisting motion rotates the greasy bits of GroEL14 away from the misfolded protein, thus radically altering the pocket lining from greasy to polar. By stretching out the protein, the chaperonin gives it a new chance to fold correctly (like untying a mistied shoelace or stretching out a tangled chain) while the changed pocket lining forces the protein's greasy bits inward just as if the protein were back in water.
In an almost completely separate process, the empty GroEL7 doughnut gives the GroES cap a nudge when it's time to release the captive protein. The cap stays put until this nudge comes, but when it comes, the protein gets ejected, ready or not, back into the environment. (If only I could get one of these chaperonins to work on my fishing reel!)
The cooperative interdependency of the GroEL and GroES proteins and the chaperoning role they take in the life of misfolded proteins reveal the enormous complexity (to say the least) of just one tiny part of a more vastly complex living system. To credit "chance" with such intricate actions and interactions seems much less reasonable than to acknowledge "intelligent design,"(4) and I only know one Designer skillful enough for the job.
1. Evelyn Strauss, "How Proteins Take Shape," Science News,
152 (1997), p. 155.
2. Hays S. Rye, et al, "Distinct Actions of cis and trans ATP within the Double Ring of Chaperonin GroEL," Nature, 388 (1997), pp. 792-798.
3. Zhaohui Xu, Arthur L. Horwich, and Paul B. Sigler, "The Crystal Structure of the Asymmetric GroEL-GroES-(ADP)-Chaperonin Complex," Nature, 388 (1997), pp. 741-750.
4. Hugh Ross, "Small-Scale Evidence of Grand-Scale Design," Facts & Faith, v. 11, n. 1 (1997), p. 1.