January 30, 2020 | David F. Coppedge

Molecular Machines Work for Us

Life runs on machinery. Here are examples of machines that keep us humming.

Molecular machine tears toxic protein clumps apart (Phys.org). When proteins get tangled up, they can not only clutter up the cell with useless molecules; they can cause serious disease. Fortunately, there is a machine that can untangle them. Called ClpB, this machine “can forcibly pull on exposed loops of protein chains, and hence extract them from protein clumps.” Sander Tans of AMOLF describes its action:

Amazing FactsTans says, “We found that the ring-shaped ClpB protein forcibly pulls loops of protein chains through its central pore. Such protein chain loops are present at the surface of protein clumps. However, these clumps are too large to pass through the pore. So through this pulling action, ClpB can extract individual protein chains from the larger aggregate. Upon removal, the protein chain can fold up again and function normally. By extracting all proteins one-by-one, the chaperone can fully untangle the entire aggregate.

Cells’ springy coils pump bursts of RNA (Phys.org). Scientists at Rice University wondered why transcription of DNA occurs in bursts instead of a steady pace. The answer has to do with the springiness of supercoils of DNA. The transcribing machine, RNA polymerase, jumps along the DNA strands in a series of springy bursts.

“We think the RNA polymerase coils DNA to start RNA production,” he said. “At the beginning of the process, you get a burst, but the process slows down as it squeezes the spring. Then gyrases come in; they untangle this supercoil so that normal production can begin again.” At the same time, he said gyrases also relieve negative stress created on the other side of the polymerase.

Modified RNA has a direct effect on DNA (Phys.org). Molecular biologists are waking up to the realization that transcription is a two-way street. As RNA polymerase reads a gene and produces a messenger RNA, the RNA has an effect on the DNA. The diagram in this article shows several machines that work with RNA polymerase in the process: a nuclease that cuts the DNA strand, a helicase that unwinds the strand, an Rnase-P and other machines that regulate the transcribed mRNA and a spliceosome that rearranges the introns and removes the exons.

‘Scrambled’ cells fix themselves (Phys.org). When intruders poke holes in a cell membrane, the cell can repair the damage. Researchers at the University of Montreal found that “cells scramble their membrane fat (lipid) into a more liquid form that allows them to fix the holes.”

Resting state structure of the hyperdepolarization activated two-pore channel 3 (PNAS). Those who enjoy diving into more detail of a molecular machine can read how scientists were able to image the resting state of a voltage-gated membrane channel. These channels are able to discriminate between very similar ions based on their electric charge. Rapid depolarization of the channel allows the action potential to travel down the membrane. The scientists found the structure of the resting state of this highly-sensitive machine.

The structure presents a chemical basis for sodium selectivity, and a constricted gate suggests a closed pore consistent with extreme voltage dependence.

Because these channels transmit signals in nerves and muscles, they are extremely important to animal life.

Update 1/31/2020: Receptors under flow: Mechanosensitive GPCRs (Medical Xpress). The diagram of this machine at the top of the article is sufficient to infer design, but there’s more evidence in its function. The seven-pointed radial symmetry of this mechanosensitive G-protein coupled receptor (GCPR) keeps us alive. Located in the membranes of our blood vessels, they respond to touch by dilating or constricting our blood vessels. Researchers at the Ludwig-Maximilan University of Munich found that “these mechanical forces activate the H1R receptor. This in turn triggers a cascade of reactions that eventually leads to dilation of the blood vessels, thus increasing the blood supply to the tissues.”

Wouldn’t it be cool to travel back in time to some of the historic philosophers and tell them about molecular machines in cells? Before Hooke and Leeuwenhoek, scientists didn’t even know that cells existed, let alone thousands of machines inside of cells. I think they would be absolutely astonished and flabbergasted to find that scientists in the year 2020 would be able to see things at a billionth of a meter, and watch molecules with moving parts doing the things that artificial machines do (and doing it faster and better). The chagrin they would feel at being so wrong about the basis of life would be overwhelmed by fascination to learn more about machines that spin and spring and pull on molecules. Darwin, though, might slink away into a dark corner and hide himself.

 

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