In new research recently published in the journal Mobile Reports, a team of scientists from the University of Massachusetts Amherst into the mysteries of how cells endure stress. Using bacterial cells, the researchers found that a damage-repairing enzyme called ClpX can not only mutate to solve multiple cellular problems, but also respond to changing levels of cellular energy to keep a cell healthy.
“What we’re really interested in,” said Peter Chien, professor of biochemistry and molecular biology at UMass Amherst and senior author of the paper, “is how cells respond to stress. We study a class of enzymes called proteases that target and destroy harmful proteins in a cell. These proteases can selectively recognize specific, individual proteins single proteins. But how do they do this? How can they choose between healthy and harmful proteins?”
To answer this question, Chien and his co-authors focused on two specific proteases, known as Lon and ClpX, each of which is exquisitely tuned to recognize a different harmful protein. For a long time, Lon and ClpX were thought to function as keys: each could only open a specific lock and no other, and if a cell had neither, serious side effects would occur.
“If you’ve ever had an extremely messy roommate in college,” Chien says, “you know how important it is to empty the trash regularly. Missing the Lon protease is like having a roommate who never washes. changes or cleans.”
But after a series of experiments that removed Lon from colonies of bacterial cells, Chien’s team began to notice something strange: Some colonies survived.
This observation led to their first discovery: ClpX can mutate to perform a Lon-like function, although it loses some of its ClpX capabilities. It’s like, in order to keep your dorm room clean, you started washing your roommate’s socks, but had to sacrifice some of your own clean laundry to do so.
By figuring out exactly how the ClpX mutation allowed the protease to expand its function, the team made their second discovery: wild, non-mutant ClpX can also perform some of Lon’s tasks, under the right conditions.
It turns out that ClpX is highly sensitive to ATP, an organic compound that is the energy source for all living cells. At normal ATP levels, ClpX focuses on its own tasks, but at a certain, lower threshold, it suddenly begins to clear up after Lon.
“This is a real breakthrough in the basic understanding of how cells work,” Chien says. “It changes the rules. Cellular energy determines not only how fast a cell works, but also how it works.”
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Samar A. Mahmoud et al, ATP hydrolysis tunes the specificity of a AAA+ protease, Mobile Reports (2022). DOI: 10.1016/j.celrep.2022.111405
Quote: Two new discoveries shed light on the mystery of how cells cope with stress (2022, September 28) retrieved September 28, 2022 from https://phys.org/news/2022-09-discoveries-mystery-cells-stress.html
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