Structure of the Peptidoglycan Synthase Activator LpoP in Pseudomonas aeruginosa

Structure. 2020 Jun 2;28(6):643-650.e5. doi: 10.1016/j.str.2020.03.012. Epub 2020 Apr 21.

Abstract

Peptidoglycan (PG) is an essential component of the bacterial cell wall and is assembled from a lipid II precursor by glycosyltransferase and transpeptidase reactions catalyzed in particular by bifunctional class A penicillin-binding proteins (aPBPs). In the major clinical pathogen Pseudomonas aeruginosa, PBP1B is anchored within the cytoplasmic membrane but regulated by a bespoke outer membrane-localized lipoprotein known as LpoP. Here, we report the structure of LpoP, showing an extended N-terminal, flexible tether followed by a well-ordered C-terminal tandem-tetratricopeptide repeat domain. We show that LpoP stimulates both PBP1B transpeptidase and glycosyltransferase activities in vitro and interacts directly via its C terminus globular domain with the central UB2H domain of PBP1B. Contrary to the situation in E. coli, P. aeruginosa CpoB does not regulate PBP1B/LpoP in vitro. We propose a mechanism that helps to underscore similarities and differences in class A PBP activation across Gram-negative bacteria.

Keywords: NMR; PBP activator; Pseudomonas; bacterial cell wall; catalysis; crystallography; enzyme; lipoprotein; structure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Catalytic Domain
  • Cell Membrane / metabolism
  • Crystallography, X-Ray
  • Lipoproteins / chemistry*
  • Lipoproteins / metabolism*
  • Models, Molecular
  • Peptidoglycan Glycosyltransferase / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Unfolding
  • Pseudomonas aeruginosa / enzymology*

Substances

  • Bacterial Proteins
  • Lipoproteins
  • Peptidoglycan Glycosyltransferase