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Peer-reviewedCC BY 4.0PLOS Biology

Structural basis for inhibition of the lipid flippase MurJ by phage lysis protein SglPP7 suggests convergent evolution with other Sgl peptides

  • Kaito Hosoda1
  • Hidetaka Kohga1
  • Sixian Wu1
  • Hiroyuki Tanaka1
  • Hideki Shigematsu2
  • Ryoji Miyazaki1
  • Min Fey Chek1
  • Tomoya Tsukazaki1
  1. 1Nara Institute of Science and Technology, Ikoma, Nara, Japan
  2. 2Diffraction and Scattering Division, Japan Synchrotron Radiation Research Institute, Sayo, Hyogo, Japan
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Abstract

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.

Bacteriophages encode lysis proteins that inhibit essential bacterial processes. This study solves the cryo-EM structure of the complex between the essential E. coli lipid II flippase MurJ and a phage lysis protein SglPP7, demonstrating that SglPP7 locks MurJ in an outward facing conformation.

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Cite

BibTeXRIS
BibTeX
@article{hosoda2026structural,
  title = {{Structural basis for inhibition of the lipid flippase MurJ by phage lysis protein SglPP7 suggests convergent evolution with other Sgl peptides}},
  author = {Kaito Hosoda and Hidetaka Kohga and Sixian Wu and Hiroyuki Tanaka and Hideki Shigematsu and Ryoji Miyazaki and Min Fey Chek and Tomoya Tsukazaki},
  journal = {PLOS Biology},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pbio.3004039},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004039},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Structural basis for inhibition of the lipid flippase MurJ by phage lysis protein SglPP7 suggests convergent evolution with other Sgl peptides
AU  - Kaito Hosoda
AU  - Hidetaka Kohga
AU  - Sixian Wu
AU  - Hiroyuki Tanaka
AU  - Hideki Shigematsu
AU  - Ryoji Miyazaki
AU  - Min Fey Chek
AU  - Tomoya Tsukazaki
PY  - 2026
DA  - 2026/10/27
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3004039
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004039
AB  - 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.  Bacteriophages encode lysis proteins that inhibit essential bacterial processes. This study solves the cryo-EM structure of the complex between the essential E. coli lipid II flippase MurJ and a phage lysis protein SglPP7, demonstrating that SglPP7 locks MurJ in an outward facing conformation.
SN  - 1545-7885
SN  - 1544-9173
ER  -