FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein

Nat Microbiol. 2019 Apr;4(4):587-594. doi: 10.1038/s41564-018-0345-x. Epub 2019 Jan 28.

Abstract

The peptidoglycan cell wall is essential for the survival and morphogenesis of bacteria1. For decades, it was thought that only class A penicillin-binding proteins (PBPs) and related enzymes effected peptidoglycan synthesis. Recently, it was shown that RodA-a member of the unrelated SEDS protein family-also acts as a peptidoglycan polymerase2-4. Not all bacteria require RodA for growth; however, its homologue, FtsW, is a core member of the divisome complex that appears to be universally essential for septal cell wall assembly5,6. FtsW was previously proposed to translocate the peptidoglycan precursor lipid II across the cytoplasmic membrane7,8. Here, we report that purified FtsW polymerizes lipid II into peptidoglycan, but show that its polymerase activity requires complex formation with its partner class B PBP. We further demonstrate that the polymerase activity of FtsW is required for its function in vivo. Thus, our findings establish FtsW as a peptidoglycan polymerase that works with its cognate class B PBP to produce septal peptidoglycan during cell division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Division
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism*
  • Peptidoglycan / metabolism*
  • Protein Binding
  • Staphylococcus aureus / cytology
  • Staphylococcus aureus / enzymology*
  • Staphylococcus aureus / genetics
  • Streptococcus thermophilus / cytology
  • Streptococcus thermophilus / enzymology*
  • Streptococcus thermophilus / genetics

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • Penicillin-Binding Proteins
  • Peptidoglycan
  • FtsW protein, Bacteria