9UKV

JM Complex - E. coli MurJ, Levivirus M lysis protein LysM (SglM)

Summary for 9UKV

• Entry DOI: 10.2210/pdb9ukv/pdb
• EMDB information: 64256
• Descriptor: Lipid II flippase MurJ, Lysis protein (2 entities in total)
• Functional Keywords: phage, lysis protein, complex, viral protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 2
• Total formula weight: 63636.30

Authors

Kohga, H.,Lertpreedakorn, N.,Tsukazaki, T. (deposition date: 2025-04-18, release date: 2025-09-10, Last modification date: 2026-03-04)

Primary citation

Kohga, H.,Lertpreedakorn, N.,Miyazaki, R.,Wu, S.,Hosoda, K.,Tanaka, H.,Takahashi, Y.S.,Yoshikaie, K.,Kuruma, Y.,Shigematsu, H.,Mori, T.,Tsukazaki, T.
Phage lysis protein Lys M acts as a wedge to block MurJ conformational changes.
Sci Adv, 11:eady8083-eady8083, 2025

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 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.

PubMed: 41061077
DOI: 10.1126/sciadv.ady8083

Experimental method

ELECTRON MICROSCOPY (3.05 Å)