AI Insight
Researchers determined the cryo-EM structure of a bacterial protein complex showing how the phage lysis protein SglPP7 inhibits MurJ, an essential enzyme in E. coli that transports lipid II across the cell membrane during cell wall synthesis. The study reveals that SglPP7 binds to MurJ and locks it in an outward-facing conformation by inserting its C-terminal tail into the protein's internal cavity, preventing normal function. Comparison with other Sgl proteins showed that despite having different sequences, these phage proteins have evolved distinct but functionally similar mechanisms to inhibit the same bacterial target.
Why it matters
Understanding how bacteriophages disable essential bacterial proteins provides insights for developing new antibacterial therapies against drug-resistant pathogens. The discovery of convergent evolution in phage lysis proteins suggests multiple viable strategies for targeting MurJ, which could inform the design of novel antibiotics.
Understand the Science
by Kaito Hosoda, Hidetaka Kohga, Sixian Wu, Hiroyuki Tanaka, Hideki Shigematsu, Ryoji Miyazaki, Min Fey Chek, Tomoya Tsukazaki
Some bacteriophages encode lysis proteins that inhibit essential bacterial processes, and elucidating their mechanisms is valuable for developing antibacterial strategies against drug-resistant pathogens. We determined the cryo-EM structure of the complex between the essential Escherichia coli lipid II flippase MurJ and the phage lysis protein SglPP7. Structural, mutational, and molecular dynamics (MD) simulation analyses revealed that SglPP7 binds along the intramembrane cleft of MurJ and inserts its C-terminal tail into the internal cavity, stabilizing MurJ in an outward-facing conformation. Structural comparison with LysM (SglM) and SglCJ3 showed that these sequence-divergent Sgl proteins stabilize MurJ in the outward-facing conformation through distinct binding modes, consistent with the possibility of convergent evolution toward MurJ inhibition.