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Developments from the Study of Cells and Molecular Machines

Intelligent design becomes increasingly apparent at the smallest scales of life as imaging improves and scientists get a closer look at the cell’s inner workings.

Dynein

Scripps Institute seeks to reveal the “structural secrets of nature’s little locomotive.” (Emphasis added.) The dynein-dynactin complex has defied analysis because “the complex’s large size, myriad subunits and high flexibility have until now restricted structural studies to small pieces of the whole.” Finer details have shown “how dynein and dynactin fit together on a microtubule, how they recruit cargoes and how they manage to move those cargoes consistently in a single direction.”

Myosin

Another locomotive protein, myosin-5, is like a tightrope walker on thin actin filaments. A news item from the University of Oxford says, “Remarkably, these proteins not only function like nano-scale lorries, they also look like a two-legged creature that takes very small steps.”

Yet the stiff-legged motion seemed awkward at first — something like a Monty Python “silly walk” sketch. But by filming the machines at 1000 frames per second, the Oxford scientists could see that the molecular machines’ motion is anything but random or silly (see the animation above). “The movement resembles the twirling of a dividing compass used to measure distances on a map,” chemist Philipp Kukura says. It’s a bigger feat than first appears. “Think of it being rather like trying to walk a tightrope in a hurricane whilst being pelted with tennis balls.”

‘We’ve uncovered a very efficient way that a protein has found to do what it needs to do, that is move around and ferry cargos from A to B,’ explains Philipp…. This study shows that if we want to build machines as efficient as those seen in nature then we may need to consider a different approach.’

It seems that if you’re designing tiny machines ‘silly’ walks may not be so silly after all.

DNA Repair Helicase

Scientists at the University of Illinois School of Engineering have, for the first time, “observed the structure and correlated function of specific proteins critical in the repair of DNA,” finding that one of the key proteins, UvrD, swivels between an open and closed state and back again. “As it turns out, the closed state unwinds the strands, using a torque wrench action. The open state allows the strands to zip together.” When in the closed position, it acts as “a ‘superhelicase’ capable of unwinding double-stranded DNA over a great distance.”

Chromatin

Intelligent design is evident in this headline from Princeton Journal Watch: “Decoding the Cell’s Genetic Filing System.” Codes? Filing systems? Indeed: five feet of DNA is packed into a tiny nucleus on tightly-wound spools of chromatin. “Access to these meticulously packed genes is regulated by post-translational modifications, chemical changes to the structure of histones that act as on-off signals for gene transcription,” the article says. Experiments to try to modify chromatin helps the Princeton team get closer to “understanding nature’s remarkable information indexing system.”

RNA Polymerase

This machine is responsible for transcribing DNA. Again, it’s a lot more sophisticated than it first appeared. Research at Harvard shows that a fairy tale about it was in the scientists’ imagination, not the cell:

Once upon a time, scientists thought RNA polymerase — the molecule that kicks off protein synthesis by transcribing DNA into RNA — worked like a wind-up toy: Set it down at a start site in our DNA and it would whir steadily along, reeling off an RNA copy, until it reached the stop site.

Lately, they’ve realized they didn’t give RNA polymerase enough credit.

“It’s more like a high-performance sports car,” said Stirling Churchman, assistant professor of genetics at Harvard Medical School. “It has to speed up, slow down and deal with obstacles in its path.”

In a one-minute video clip, Churchman explains why she is excited about the research, bringing at least a little clarity to a situation that often leaves her “overwhelmed by how complex it is,” yet still manages to do its job. Her team found “a lot going on” as the machine proceeds down the DNA strand. The “sports cars” even know how to slow down for “speed bumps” and avoid head-on collisions. “Ultimately, it emphasizes the simplicity of our current views of how transcription occurs,” Churchman says.

Ribosome

Ribosomes process messenger RNA and translate it into protein. An article from CNRS (Institut de G�n�tique et de Biologie Mol�culaire et Cellulaire) at the University of Strasbourg tells how French scientists mapped the complete human ribosome (all 220,000 atoms), including both subunits, at 3-angstrom resolution. The new model, much more detailed now than the simple animation in Illustra’s 2002 documentary Unlocking the Mystery of Life, is bound to increase admiration of this “molecular nanomachine” so important to genetics. One finding so far: “after delivering the amino acids they are carrying, transfer RNA continue to interact with the ribosome at a specific site (the tRNA exit site).”

Incidentally, the April 24 issue of Science has a special section on “The delicate dance of translation and folding,” with research papers about how the cell gets from messenger RNA to folded protein.

Lysosomes

Even the cleanup crew deserves our admiration. Current Biology produced a “Quick Guide” to lysosomes in the April 20 issue. Making up 5 percent of the cell’s volume, lysosomes can break down a “wide variety of macromolecules” delivered to them by various pathways. Much more than “cell stomachs,” though, these machines participate in the cell’s signaling networks, membrane repair and defense against parasites. To maintain their acid requirement of pH < 5, they employ rotary machines similar to ATP synthase that pump protons into the interior. Lysosomes may also prove to be a fountain of youth: “Increased life span is the result of lysosomal production of the bioactive lipid oleoylethanolamide, which is translocated into the nucleus by a chaperone protein and affects the transcription of genes that regulate longevity.”

Centrioles

Centrioles are involved in winching apart the chromosomes into the daughter cells. New findings announced by the Ecole Polytechnique Federale de Lausanne are of interest from an ID perspective: these molecular structures appear to be carriers of information outside of the genome. In the zygote, centrioles (which resemble the machines in cilia) are inherited from the father only. By tagging these paternal centrioles, the scientists found that they persist through at least ten cell divisions: “Even more intriguing are the implications the study has for biology at large, as it raises the possibility that centrioles, persisting across several cell cycles, could effectively be a non-genetic information carrier,” the article says. “If this were confirmed, it could represent a paradigm shift in the way we think and understand the biology of an organelle that has been present across eukaryotic evolution.

Well, maybe not evolution. Since they have not evolved in all that time, we can think and understand them better as products of intelligence. That certainly makes sense of all these amazing molecular machines. If machines look better designed the closer you look, ID must be on the right track.

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