Plate Nº 69 · recorded November 11, 2026
Biology & EvolutionReported finding
Three phage proteins lock bacterial transporter MurJ in place
A 2026 PLOS Biology study finds that SglPP7, LysM and SglCJ3 stabilize a similar outward-facing shape of MurJ, potentially offering a structural blueprint for targeted antibacterial drug design.
By Marcus Bennett4 min read752 words
In brief
- A 2026 PLOS Biology study compared three MurJ inhibitors: SglPP7, LysM and SglCJ3.
- All three stabilized a similar outward-facing conformation of MurJ despite different binding arrangements.
- SglPP7 binds along a lipid-binding groove and inserts a short C-terminal tail into a deep internal cavity.
- Researchers combined cryo-electron microscopy, targeted mutations, bacterial lysis experiments and computer simulations.
- The paper's DOI is 10.1371/journal.pbio.3004039.
By Marcus Bennett
Three known phage proteins can inhibit the same bacterial transporter, MurJ, according to a 2026 PLOS Biology study led by Nara Institute of Science and Technology (NAIST) researchers in Japan. Cryo-electron microscopy resolved how SglPP7 binds MurJ. Comparisons with LysM and SglCJ3 showed that all three stabilize a similar outward-facing structure despite different binding arrangements.
What problem did the study tackle?
Drug-resistant bacteria are becoming more common worldwide, creating a major public health challenge. Finding new ways to eliminate them requires researchers to identify essential bacterial processes that future antibiotics can target.
Bacteriophages, or phages, are viruses that infect bacteria and commandeer their cellular machinery to replicate. Some phages inject small proteins that shut down specific bacterial processes and kill the cell. One such target is MurJ, a protein bacteria use to transport lipids needed to build their cell wall.
Researchers had already found several phage proteins that inhibit MurJ, although their amino acid sequences—the ordered building blocks of proteins—varied considerably. That raised a specific question: can proteins with different sequences block the same transporter, and do they use the same molecular strategy?
In short, the study tested whether different natural inhibitors converge on one essential bacterial transport mechanism.
How did the researchers examine the complex?
Assistant Professor Hidetaka Kohga led the team, which examined how the phage protein SglPP7 inhibits MurJ and compared its mechanism with those of other phage inhibitors. The researchers used cryo-electron microscopy, a technique that reveals biological molecules at near-atomic resolution, to determine the structure of the MurJ–SglPP7 complex, meaning the two proteins bound together.
They combined that structure with three lines of experimental work:
- Targeted protein mutations: Researchers made deliberate changes to selected amino acids to test which interactions mattered.
- Bacterial lysis experiments: They examined cell rupture as a functional test of the interaction's effect on bacteria.
- Computer simulations: They modeled how SglPP7 changes MurJ's behavior.
Co-authors include Kaito Hosoda, Sixian Wu, Hiroyuki Tanaka, Dr. Hideki Shigematsu, Assistant Professor Ryoji Miyazaki, Associate Professor Min Fey Chek and Professor Tomoya Tsukazaki, all from NAIST.
Together, the structural and cellular experiments connect SglPP7's contact points with MurJ's loss of transport activity.
What does SglPP7 do to MurJ?
SglPP7 lies along the lipid-binding groove in MurJ and inserts its short C-terminal tail into a deep internal cavity, or pocket. The C-terminal tail is the end of the protein's amino-acid chain. Together, these contacts stabilize MurJ in an outward-facing conformation—one structural orientation that cannot complete the back-and-forth changes required for lipid transport.
Kohga said: "These findings suggest convergent evolution toward a common target through diverse inhibitory mechanisms." In plain terms, convergent evolution means different phage proteins have evolved to produce the same overall effect on MurJ.
Put simply, SglPP7 inhibits MurJ by locking the transporter into a shape that cannot cycle normally.
Do other phage proteins use the same strategy?
Researchers compared SglPP7 with two other known phage proteins, LysM and SglCJ3. Despite their different binding arrangements, all three stabilized a similar overall conformation of MurJ. Their amino acid sequences and contact points differ, but the resulting inhibition converges.
Understanding these interactions could help researchers design new drugs and engineer artificial phage proteins with targeted antibacterial activity. Kohga said that revealing how phage proteins inhibit MurJ provides a foundation for drug discovery targeting this transporter. Further research on naturally evolved antibacterial mechanisms may clarify how phages disable bacterial processes and bring future antibiotics closer.
Different phage proteins can disable MurJ without sharing the same binding arrangement.
What could the result enable?
"Although still at the basic research stage, these findings could contribute to the development of new antibacterial agents against drug-resistant bacteria," Kohga said. The result identifies a molecular mechanism and a starting point for design, rather than a finished antibacterial medicine.
The immediate contribution is a molecular blueprint for antibacterial design, not a ready-made drug.
Where is the study available?
The paper is titled "Structural basis for inhibition of the lipid flippase MurJ by phage lysis protein SglPP7 suggests convergent evolution with other Sgl peptides." First author Kaito Hosoda and colleagues published it in PLOS Biology in 2026; its DOI is 10.1371/journal.pbio.3004039.
The full structural, mutation, lysis and simulation work is documented in the journal article.
For now, researchers have a detailed map of a bacterial vulnerability; converting that map into an effective antibacterial remains the next stage.
via phys.org/rss-feed/ (Source)
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News editor covering regulation, policy and their impact on general science news at SciBeat.
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