Biological complexity: automatic cellular switches (Introduction)

by David Turell , Tuesday, November 15, 2016, 00:00 (2931 days ago) @ David Turell

Cells manufacture at a high rate and they use switches to change activities in which molecules act automatically. This is a study of a bacterial switch:

http://phys.org/news/2016-11-x-ray-laser-real-time-snapshots-chemical.html

"And because this particular type of RNA switch, known as a riboswitch, is found only in bacteria, a deeper understanding of its function may offer a way to turn off protein production and kill harmful germs without causing side effects in the humans they infect.

"'Previous experiments at SLAC's X-ray laser have studied biological reactions like photosynthesis that are triggered by light. But this is the first to observe one that is triggered by the chemical interaction of two biomolecules in real time and at the atomic scale," said Yun-Xing Wang, a structural biologist

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"both DNA and RNA also contain extensive regions that don't code for any protein - the so-called genetic "dark matter." Scientists thought for many years that these regions didn't do anything. Now they know that they play an important role in determining where and when genes turn on and off and otherwise fine-tuning their function.

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"Wang's team studied a riboswitch from Vibrio vulnificus, a bacterium related to the one that causes cholera. The riboswitch sits in a long strand of messenger RNA (mRNA), which copies DNA's instructions for making a protein so they can be read and carried out by the ribosome. The switch acts like a thermostat that regulates protein production

"In this case, the mRNA guides production of a protein that in turn helps to produce a small molecule called adenine. When there is too much adenine in the bacterial cell, adenine molecules enter pockets in the riboswitches and flip the riboswitches into a different shape, and this changes the pace of protein and adenine production.

"For the LCLS experiments, the researchers made nanocrystals that incorporated millions of copies of the riboswitch and mixed them with a solution containing adenine molecules. Each crystal was so small that adenine could quickly and uniformly penetrate into every corner of it, enter riboswitch pockets and flip them almost instantaneously, as if they were millions of synchronized swimmers executing a single flawless move.

"The scientists took snapshots of this interaction by hitting the crystals with X-ray laser pulses at carefully timed intervals after the mixing started. This gave them the first glimpse of a fleeting intermediate stage in the process, which occurred 10 seconds in. Separately, they obtained the first images of the riboswitch in its initial, empty-pocket state, and discovered that it existed in two slightly different configurations, only one of which participates in switching.

"The researchers were surprised to discover that the sudden change in the shape of the riboswitches was so dramatic that it changed the shape of the entire crystal, too. Normally a major change like this would crack the crystal and spoil the experiment. But because these crystals were so small they held together, so the X-ray laser could still get structural information from them."

Comment: This is a beautiful piece of research into how a piece of cellular machinery works. Be sure to look at the diagrams. Note this is in the 'junk' DNA area. Certainly as research advances most of the junk designation areas will disappear.