Biology subjects

Lertpreedakorn, N.

Publications and source records attributed to Lertpreedakorn, N..

2 recordsLinked to original sources

bioRxiv2025

Phage lysis protein LysM acts as a wedge to block MurJ conformational changes

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 [A] 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 MurJs 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.

molecular biology↗

bioRxiv2023

Critical residues of the antibiotic peptide LysM that inhibits lipid II flipping

Small single-strand DNA/RNA phages that infect gram-negative bacteria encode lysis proteins that induce cell lysis without directly degrading the cell wall. One such protein, the 37-residue LysM protein derived from a lysis gene of Levivirus phage M (lysM), completely blocks the lipid II transport activity mediated by Escherichia coli MurJ, which is essential for peptidoglycan biosynthesis. LysM was proposed to be a single -helical transmembrane protein that binds to MurJ and prevents its conformational transition during lipid II transport. Although LysM possibly interacts with MurJ, the inhibition mechanism remains unclear. Here, we identified the crucial residues for LysM function via comprehensive alanine-scanning mutagenesis. These residues were located on two surfaces in an -helix model, probably providing surfaces interacting with MurJ in the membrane. This study provides fundamental information regarding the mechanism of LysM inhibition.

microbiology↗