Cell's Molecular Machines Arouse Fascination
With increasing image quality at their disposal, biologists are finding amazing molecular machines at work in living cells.
Spark plugs: Biochemists have known for a long time that ATP powers most chemical reactions in the cell, but how does it work? There has to be a “spark plug” of sorts to put it over the energy barrier, a press release from Heidelberg University explains:
Biomolecular motors are protein molecules responsible for mechanical movement in cells. These smallest of known motors use the molecule adenosine triphosphate (ATP) as fuel, which all living organisms use as a source of energy for processes that require it. In order to understand how these cell motors use ATP to function, they can be compared to an automobile engine, in which energy is released by burning petrol. Because petrol does not ignite by itself, energy must be applied to initiate the combustion reaction. This job is done by the spark plug. Energy is not released until the heat energy of the spark is applied to overcome the energy barrier of petrol combustion. According to Stefan Fischer, there are a number of parallels to biomolecular motors. The ATP molecule is stable and like petrol does not release its energy spontaneously. Whereas ATP splits rather than burns, there is also an energy barrier that must be crossed to trigger that splitting, known as hydrolysis.
Careful study of the myosin motor revealed the spark plug. Out of near-infinite combinations of orientations in the 600 atoms of myosin, one spot forms a precise fit in a certain pocket. This fit is able to lower the energy and split the ATP into ADP and phosphate: “the electrostatic charges on the protein atoms are positioned around the ATP in such a way that they modify the electron density of this molecule, making it easier for the ATP fuel to split,” they found. Because the action takes place in a trillionth of a second, advanced computing techniques applied to quantum mechanics were required to catch it. The universality of ATP hydrolysis in living organisms suggests that many other molecular machines use this “biological spark plug mechanism” in their operations.
DNA sunscreen: UV light can damage DNA molecules and cause serious genetic defects. As a protective mechanism, DNA is able to capture stray electrons displaced by radiation, and toss them right back, according to a report in Medical Xpress about research done at Montana State University. “The back-and-forth motion of the electron explains how DNA remains undamaged most of the time,” the article says. “At the same time, the researchers note that the transferred electron could be used to repair damage in a way that mimics how certain repair proteins fix UV damage.” The electron handshake takes place in femtoseconds (a femtosecond is a millionth of a billionth of a second). The article describes some of the equipment used to make this discovery:
The instrument they used takes up most of a room in MSU’s Chemistry and Biochemistry Building. It incorporates black boxes, mirrors, stacked razor blades, tiny plastic tubes and what looks like a fish tank, with every component having a purpose and a place on the steel optical tables that hold them. The razor blades, for example, block laser beams. The mirrors direct light to the “fish tank,” which holds DNA samples. The air inside the tank is drier than any desert so it won’t contain the water vapor or carbon dioxide that could interfere with experiments.
Trash ID: Biochemists have known that proteins targeted for degradation carry tags of a molecule called ubiquitin (because it’s ubiquitous in the cell). The proteasome reads this tag and knows what to destroy. In stem cells, however, these poly-U chains could cause the cell to lose its stemness. How does the cell know which tags to act on, and which to ignore? Sometimes the tag itself needs to go in the trash! A press release from Cold Spring Harbor Laboratory shows a diagram of a protein named Dis3l2 that reads each tag, like a sorter, and shreds the ones needing to be ignored:
Dis3l2 is a molecular machine that helps to preserve the character of stem cells. It serves as the executioner of an elegant pathway that prevents stem cells from changing into other cell types. The protein does this by acting like a garbage disposal for messages in the cell, cutting them up until they no longer encode useful information. But Dis3l2 is necessarily highly specific. While it must degrade messages that would alter the fate of the stem cell, discarding the wrong message could have devastating consequences.
Therefore, Dis3l2 only targets specific messages that have been marked with a molecular flag, known as a “poly-U” chain. The enzyme ignores the majority of messages in the cell – those that go on to encode proteins and other critical messages – whose ends are decorated with a different type of chain, called “poly-A” tail.
The diagram shows the poly-U tail fitting like a hand in a funnel-shaped pocket in the Dis3l2 machine, making more than a dozen atomic contacts. “Together, all of these points create a sticky web that holds the poly-U sequence deep within the enzyme,” says Faehnle. “But other chains don’t interact – they can slide right out.” That’s how this precision machine differentiates between good messages and ones to be shredded. Defects in the reader could lead to cancer, the article points out.
A PIN for dynein: Science Magazine reported that the cargo-carrier machine dynein is inactive in the cell until three “adaptor proteins,” act like a personal identification number (PIN) to turn it on. It’s “One, two, three, cytoplasmic dynein is go!” Viki Allan’s Perspective piece on this discovery says in the same issue of Science.
The ribosome square dance: The ribosome improves the efficiency of its translation process by dancing with its partners as it reads the messenger RNA to make proteins. The title of the paper in PNAS reads: “The ribosome uses cooperative conformational changes to maximize and regulate the efficiency of translation.” The abstract says, “Our findings suggest that such coordination is likely to be a general and important mechanism through which all biomolecular machines maximize and regulate their functional efficiencies.”
Ambidextrous chaperone: Can the beautiful Gro-EL chaperone, which helps proteins fold, only take in polypeptides made of the normal left-handed amino acids? No, researchers at Utah State, publishing in PNAS, found. It doesn’t discriminate. It will let right-handed proteins into the dressing room just as well, proving it “reveals ambidextrous chaperone activity.”
Suspended license: The centrosome is a “fascinating single copy organelle” that acts as the “microtubule organizing center” during mitosis. Cell division passes a number of checkpoints to proceed. Each organelle, including the centrosome, needs a license to duplicate itself at the Spindle Assembly Checkpoint. In a paper titled “Centrosome Duplication: Suspending a License by Phosphorylating a Template,” Current Biology describes how “The phosphorylation status of Sfi1, a structural component of the yeast centrosome, governs the centrosome duplication cycle, raising the possibility that licensing of centrosome duplication occurs by modulating Sfi1, which potentially acts as a template for a new centrosome.”
Membrane voltmeter: You’ll find electrical-engineering lingo in a paper on PNAS. Scientists from USC with colleagues tried to figure out how to measure voltage differences in membrane proteins. “Determining voltage changes in response to charge separation within membrane proteins offers fundamental information on mechanisms of charge transport and displacement processes,” they say of their work that attempted the “extremely challenging” measurements.
Surveillance before separation: One of the most eye-catching parts of cell division under a microscope is when the chromosomes are physically pulled apart into the daughter cells. Science Magazine described a “feedback control of chromosome separation” at that critical stage. It works by means of a “gradient” of a molecule named Aurora B that continuously monitors the degree of separation between the sister chromatids. The chromatids must reach a checkpoint before nuclear envelope degradation (NER) is allowed to proceed. “Thus, an Aurora B gradient appears to mediate a surveillance mechanism that prevents chromosome decondensation and NER until effective separation of sister chromatids is achieved,” the abstract says. “This allows the correction and reintegration of lagging chromosomes in the main nuclei before completion of NER.”
So much exquisite control in every part of the cell! Nothing is left to chance. Everything is regulated and monitored, with amazing precision. How can anyone believe that these processes resulted from blind, unguided natural causes by mistake? The details of these molecular machines at work should send such notions to the wastebin of discarded follies.
This is only a glimpse. Your poor editor would be denied sleep trying to report on all the findings pouring forth from the journals. Most have nothing to say about how these wonders might have evolved. At CEH, we’re doing the condensing work of these important findings, translating them from scientific jargon, so that you can get the word out to your friends and contacts. Such knowledge can hasten the overdue death of Darwinism.