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-Structure paper
| Title | Phage lysis protein Lys acts as a wedge to block MurJ conformational changes. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 11, Issue 41, Page eady8083, Year 2025 |
| Publish date | Oct 10, 2025 |
Authors | Hidetaka Kohga / Napathip Lertpreedakorn / Ryoji Miyazaki / Sixian Wu / Kaito Hosoda / Hiroyuki Tanaka / Yutaro S Takahashi / Kunihito Yoshikaie / Yutetsu Kuruma / Hideki Shigematsu / Takaharu Mori / Tomoya Tsukazaki / ![]() |
| PubMed Abstract | Many antibiotics target essential cellular processes. To combat multidrug-resistant bacteria, new antibacterial strategies are needed. In the peptidoglycan biogenesis pathway in , MurJ, the lipid II ...Many antibiotics target essential cellular processes. To combat multidrug-resistant bacteria, new antibacterial strategies are needed. In the peptidoglycan biogenesis pathway in , MurJ, the lipid II flippase, is an essential membrane protein. The 37-residue protein M from the phage, known as Lys or Sgl, targets MurJ and induces cell lysis; however, its molecular mechanism remains unclear. Here, we present the cryo-EM structure of the MurJ/Lys (JM) complex at 3.09-angstrom resolution, revealing that Lys interacts with the crevasse between TM2 and TM7 of MurJ, locking MurJ in an outward-facing conformation, with Lys acting like a wedge. Alanine-scanning mutagenesis and pull-down assays revealed key residues responsible for Lys function, and molecular dynamics simulations showed that Lys stabilizes MurJ's outward-facing state. These findings demonstrate an unprecedented phage-derived mechanism for blocking lipid II transport, providing a structural framework for designing MurJ-targeted antimicrobial agents. |
External links | Sci Adv / PubMed:41061077 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.05 Å |
| Structure data | EMDB-64256, PDB-9ukv: |
| Source |
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Keywords | VIRAL PROTEIN / Phage / Lysis protein / Complex |
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enterobacteria phage m (virus)
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