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TitleStructures of the lipid II flippase from the monoderm pathogen Staphylococcus aureus.
Journal, issue, pagesJ Biol Chem, Page 113516, Year 2026
Publish dateSep 5, 2026
AuthorsYancheng E Li / Grace F Baron / William M Clemons /
PubMed AbstractPeptidoglycan biogenesis requires membrane flippases to translocate lipid-linked precursors across the cytoplasmic membrane for processing. This essential step is mediated by MurJ, the lipid II ...Peptidoglycan biogenesis requires membrane flippases to translocate lipid-linked precursors across the cytoplasmic membrane for processing. This essential step is mediated by MurJ, the lipid II flippase conserved across all peptidoglycan-producing bacteria. While MurJ from diderm bacteria has been structurally resolved in multiple conformational states, its monoderm homolog remains uncharacterized. Monoderm MurJ homologs exhibit substantial sequence divergence yet retain the same lipid II flipping function and are promising antibiotic targets. Here we report structures of Staphylococcus aureus MurJ (SaMurJ) captured in both outward- and inward-facing conformations. These structures show that SaMurJ adopts the conserved MOP family fold and undergoes conformational transitions consistent with an alternating-access mechanism. Our findings reveal conserved and divergent features of MurJ between diderm and monoderm bacteria that are critical for lipid II flipping and provide a structural framework for probing substrate recognition and specific inhibition.
External linksJ Biol Chem / PubMed:42700959
MethodsEM (single particle)
Resolution3.5 - 3.9 Å
Structure data

76175

11xx

EMDB-76175, PDB-11xx:
Staphylococcus aureus MurJ in the outward-facing conformation
Method: EM (single particle) / Resolution: 3.6 Å

76176

11xy

EMDB-76176, PDB-11xy:
Escherichia coli MurJ in the outward-facing conformation
Method: EM (single particle) / Resolution: 3.9 Å

76177

11xz

EMDB-76177, PDB-11xz:
Staphylococcus aureus MurJ in the inward-facing conformation
Method: EM (single particle) / Resolution: 3.5 Å

76178

11ya

EMDB-76178, PDB-11ya:
Staphylococcus aureus MurJ R176A mutant
Method: EM (single particle) / Resolution: 3.6 Å

Source
  • Staphylococcus aureus (bacteria)
  • staphylococcus aureus (strain nctc 8325 / ps 47) (bacteria)
  • Escherichia coli K-12 (bacteria)
  • escherichia coli (E. coli)
KeywordsTRANSPORT PROTEIN / lipid II flippase / peptidoglycan biosynthesis

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