Reference - Detail
| RRC ID | 89073 |
|---|---|
| Author | Kohga H, Lertpreedakorn N, Miyazaki R, Wu S, Hosoda K, Tanaka H, Takahashi YS, Yoshikaie K, Kuruma Y, Shigematsu H, Mori T, Tsukazaki T. |
| Title | Phage lysis protein LysM acts as a wedge to block MurJ conformational changes. |
| Journal | Sci Adv |
| Abstract |
Many antibiotics target essential cellular processes. To combat multidrug-resistant bacteria, new antibacterial strategies are needed. In the peptidoglycan biogenesis pathway in Escherichia coli, MurJ, the lipid II flippase, is an essential membrane protein. The 37-residue protein M from the Levivirus phage, known as LysM or SglM, targets MurJ and induces cell lysis; however, its molecular mechanism remains unclear. Here, we present the cryo-EM structure of the MurJ/LysM (JM) complex at 3.09-angstrom resolution, revealing that LysM interacts with the crevasse between TM2 and TM7 of MurJ, locking MurJ in an outward-facing conformation, with LysM acting like a wedge. Alanine-scanning mutagenesis and pull-down assays revealed key residues responsible for LysM function, and molecular dynamics simulations showed that LysM 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. |
| Volume | 11(41) |
| Pages | eady8083 |
| Published | 2025-10-10 |
| DOI | 10.1126/sciadv.ady8083 |
| PMID | 41061077 |
| PMC | PMC12506998 |
| MeSH | Bacteriophages* / metabolism Cryoelectron Microscopy Escherichia coli / metabolism Escherichia coli / virology Escherichia coli Proteins* / chemistry Escherichia coli Proteins* / genetics Escherichia coli Proteins* / metabolism Molecular Dynamics Simulation Protein Binding Protein Conformation Viral Proteins* / chemistry Viral Proteins* / genetics Viral Proteins* / metabolism |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 60 |
| Altmetric score changes over past 6months | 2.7 |
| Resource | |
| General Microbes | JCM1465 JCM20135 |