Protein biosynthesis—the process by which cells produce the proteins essential for life and growth—is a complex and tightly regulated process. An interdisciplinary team led by LMU biologist PD Dr. Jürgen Lassak has uncovered a previously unknown mechanism bacteria use to regulate this process.
According to findings published in Nature Communications, a protein called EfpL acts as a regulator of protein synthesis, increasing or decreasing activity in response to cellular metabolism. This discovery reveals new insights into how bacteria dynamically adapt their protein production.
During protein biosynthesis, cells face a challenge in incorporating the amino acid proline into growing protein chains. Proline’s rigid structure often causes stalling at the ribosomes—the cell’s “protein factories.” To overcome this, bacteria rely on a factor known as EF-P, which facilitates proline incorporation into ribosomes.
The team discovered that certain bacteria also use a protein called EfpL, closely related to EF-P, as an additional tool for protein synthesis. However, unlike EF-P, EfpL adjusts its activity based on the cell’s metabolic state, using specific chemical modifications to fine-tune protein production as needed.
“EfpL offers a unique opportunity to understand the flexible adaptation of bacterial protein production to environmental conditions. This type of regulation was previously unknown, and we have shown for the first time that the metabolism of the cell influences the activity of EfpL,” said Alina Sieber, study lead author from Ludwig-Maximilians-Universität München.
Notably, many human pathogens, including Salmonella species, Escherichia coli, and the bacteria responsible for cholera and plague, utilize EfpL. The researchers hypothesize that EfpL’s precise control of protein synthesis helps bacteria adapt to changing environments, such as during human infection. Blocking EfpL could provide a new strategy for preventing these infections and developing innovative treatments.
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Journal reference:
Sieber, A., et al. (2024) EF-P and its paralog EfpL (YeiP) differentially control the translation of proline-containing sequences. Nature Communications. doi.org/10.1038/s41467-024-54556-9.