Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane

• Published in: The EMBO journal Vol. 30; no. 8; pp. 1425 - 1432
• Main Authors: Mohammadi, Tamimount, van Dam, Vincent, Sijbrandi, Robert, Vernet, Thierry, Zapun, André, Bouhss, Ahmed, Diepeveen-de Bruin, Marlies, Nguyen-Distèche, Martine, de Kruijff, Ben, Breukink, Eefjan
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 20.04.2011; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: antibiotic target; Bacteria; Bacterial Proteins - metabolism; Biological Transport; Cell Membrane - metabolism; Cell Wall - metabolism; cell wall synthesis; Cells; E coli; EMBO05; EMBO20; Escherichia coli; Escherichia coli - metabolism; flippase activity; FtsW; Lipid II; Lipids; Membrane Lipids - metabolism; Membrane Proteins - metabolism; Membranes; Peptidoglycan - metabolism; Recombinant Proteins - metabolism; Translocation; antibiotic target; Lipid II; FtsW; cell wall synthesis; flippase activity
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2011.61

Bacterial cell growth necessitates synthesis of peptidoglycan. Assembly of this major constituent of the bacterial cell wall is a multistep process starting in the cytoplasm and ending in the exterior cell surface. The intracellular part of the pathway results in the production of the membrane‐anchored cell wall precursor, Lipid II. After synthesis this lipid intermediate is translocated across the cell membrane. The translocation (flipping) step of Lipid II was demonstrated to require a specific protein (flippase). Here, we show that the integral membrane protein FtsW, an essential protein of the bacterial division machinery, is a transporter of the lipid‐linked peptidoglycan precursors across the cytoplasmic membrane. Using Escherichia coli membrane vesicles we found that transport of Lipid II requires the presence of FtsW, and purified FtsW induced the transbilayer movement of Lipid II in model membranes. This study provides the first biochemical evidence for the involvement of an essential protein in the transport of lipid‐linked cell wall precursors across biogenic membranes. This study identifies FtsW as the flippase that translocates lipid‐linked peptidoglycan precursors across the cell membrane during bacterial cell wall synthesis.