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bioRxiv · 10.1101/2023.05.22.541694

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

Kohga, H.·Lertpreedakorn, N.·Miyazaki, R.·Tsukazaki, T.
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Abstract

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.

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Kohga, H., Lertpreedakorn, N., Miyazaki, R., Tsukazaki, T.. 2023-05-22. Critical residues of the antibiotic peptide LysM that inhibits lipid II flipping. https://doi.org/10.1101/2023.05.22.541694

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