In UMass Amherst, researchers claim to have made a significant advancement in our understanding of how cells respond to a stressful environment. The scientists found out that a damage-fixing enzyme named ClpX may adapt to fluctuating degrees of cellular unit energy to maintain cell health as well as mutate to remedy a variety of cellular units applying bacteria. The study was released in Cell Reports.
How do cells react to stressful conditions?
Two distinct proteases—Lon and ClpX—each of which is programmed to detect a different damaging protein—were the focus of the research. Long believed to act as locks, these proteases could only unlock one type of lock at a time, and if either were missing from a cell, negative side effects would appear.
AAA+ proteases in bacteria, such Lοn and ClpΧP, break down substrates with great selectivity. These devices use the ATP hydrolysis energy to drive the unfolding and destruction of their target substrates. Here, we demonstrate that a mutation in the ATP binding site of ClpΧ changes protease specificity to facilitate decline of substrates that are typically Lon-restricted.
However, this ClpX mutant performs poorer at destroying ClpXP targets, indicating a simple way to change a protease’s preferred substrate balance. In vitro, wild-type ClpΧP similarly to the shifting selectivity of mutant ClpΧP, which has changed ATP hydrolysis kinetics, degrades Lon-restricted substrates more quickly when ATP levels are decreased. These findings lead us to hypothesize that ATP hydrolysis rates adjust protease selectivity in addition to driving substrate unfolding and decline.
The team of scientists conducted a series of studies in which they deleted Lon from a group of bacteria derived from the same mother cell, and as a result, some of them appeared to survive. They observed that ClpX can change to carry out a Lon functions, although it loses some of its ClpX characteristics.
The team’s another finding was that, under the correct circumstances, wild ClpX can also carry out some of Lon’s responsibilities. This was discovered while determining precisely how the ClpΧ modification permitted the protease to broaden its functions.
As found out, ClpΧ is sensitized to ATP, the chemical substance that provides all cells with their energy. ClpΧ concentrates on its responsibilities when ATP levels are good, but if insufficient, it abruptly cleans up after Lοn. This is a significant advance in our fundamental knowledge of how cells function.
