Waste collectors collect and dispose of household waste. In cells, a similar process works to eliminate damaged and potentially hazardous proteins. A new study published in the Science Advances journal offers better insights into how this process occurs.
Increasing temperature breaks the molecular bond between two DegP units and initiates their proteolytic activity. Image Credit: Johannes Thomas.
Proteases are used by cells for housekeeping quite similar to how waste collectors dispose of household waste.
Think about what happens when waste collectors go on strike in a big city. Similarly, a non-functioning waste collection system in a cell can lead to chaos when damaged proteins accumulate. This could allow serious diseases to develop.”
Björn M. Burmann, Senior Lecturer and Researcher in Chemistry, University of Gothenburg
Burmann is also the team leader for the researchers who contributed to this study.
Neutralizes harmful proteins
The single-cell bacterium Escherichia coli served as a model system to the researchers to gain better insights into how proteases maintain cells clean. This bacterium is found in the human intestine adapted to thrive in different stressful environmental conditions.
One of the waste collection disposal workers in the bacterial cell is the enzyme DegP, a protease that can eliminate unstable and harmful proteins by shredding them into pieces and thus prevent them from building up in the cell.”
Darius Šulskis, Study Principal Author, University of Gothenburg
Šulskis is a doctoral student in Björn M. Burmann’s research group.
Temperature switches activate response
To date, there was no knowledge on what triggered DegP. However, in the study, Darius Šulskis shows that DegP is triggered by a switch in temperature regulated at a molecular level. DegP stays inactive at low temperatures but gets triggered at higher temperatures. This initiates the process of waste disposal in the cell, thereby disposing of harmful waste.
Understanding this built-in cleaning mechanism means that it can be used in medical research and be important for future medical applications.”
Björn M. Burmann, Senior Lecturer and Researcher in Chemistry, University of Gothenburg
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Journal reference:
Šulskis, D., et al. (2021) Structural basis of DegP protease temperature-dependent activation. Science Advances. doi.org/10.1126/sciadv.abj1816.