Elongated structure of the outer-membrane activator of peptidoglycan synthesis LpoA: implications for PBP1A stimulation

Structure. 2014 Jul 8;22(7):1047-54. doi: 10.1016/j.str.2014.04.017. Epub 2014 Jun 19.


The bacterial cell envelope contains the stress-bearing peptidoglycan layer, which is enlarged during cell growth and division by membrane-anchored synthases guided by cytoskeletal elements. In Escherichia coli, the major peptidoglycan synthase PBP1A requires stimulation by the outer-membrane-anchored lipoprotein LpoA. Whereas the C-terminal domain of LpoA interacts with PBP1A to stimulate its peptide crosslinking activity, little is known about the role of the N-terminal domain. Herein we report its NMR structure, which adopts an all-α-helical fold comprising a series of helix-turn-helix tetratricopeptide-repeat (TPR)-like motifs. NMR spectroscopy of full-length LpoA revealed two extended flexible regions in the C-terminal domain and limited, if any, flexibility between the N- and C-terminal domains. Analytical ultracentrifugation and small-angle X-ray scattering results are consistent with LpoA adopting an elongated shape, with dimensions sufficient to span from the outer membrane through the periplasm to interact with the peptidoglycan synthase PBP1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Hydrogen-Ion Concentration
  • Lipoproteins / chemistry*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Penicillin-Binding Proteins / chemistry*
  • Penicillin-Binding Proteins / metabolism
  • Peptidoglycan / biosynthesis*
  • Periplasm / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Scattering, Small Angle
  • Sequence Homology, Amino Acid
  • Temperature
  • X-Ray Diffraction


  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Lipoproteins
  • LpoA protein, E coli
  • Penicillin-Binding Proteins
  • Peptidoglycan

Associated data

  • PDB/2MHK