Induced conformational changes activate the peptidoglycan synthase PBP1B

Alexander J F Egan, Roberto Maya-Martinez, Isabel Ayala, Catherine M Bougault, Manuel Banzhaf, Eefjan Breukink, Waldemar Vollmer, Jean-Pierre Simorre

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
184 Downloads (Pure)

Abstract

Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer consisting of glycan chains linked by short peptides into a mesh-like structure. Growing and dividing cells expand their PG layer using inner-membrane anchored PG synthases, including Penicillin-binding proteins (PBPs), which participate in dynamic protein complexes to facilitate cell wall growth. In Escherichia coli, and presumably other Gram-negative bacteria, growth of the mainly single layered PG is regulated by outer membrane-anchored lipoproteins. The lipoprotein LpoB is required to activate PBP1B, which is a major, bi-functional PG synthase with glycan chain polymerizing (glycosyltransferase) and peptide cross-linking (transpeptidase) activities. In this work we show how the binding of LpoB to the regulatory UB2H domain of PBP1B activates both activities. Binding induces structural changes in the UB2H domain, which transduce to the two catalytic domains by distinct allosteric pathways. We also show how an additional regulator protein, CpoB, is able to selectively modulate the TPase activation by LpoB without interfering with GTase activation. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)335-356
Number of pages22
JournalMolecular Microbiology
Volume110
Issue number3
Early online date25 Oct 2018
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Peptidoglycan
  • Penicillin‐binding protein
  • Lipoprotein
  • NMR structure
  • Allostery

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