Induced conformational changes activate the peptidoglycan synthase PBP1B. Issue 3 (25th October 2018)

• Record Type: Journal Article
• Authors: Egan, Alexander J. F.; Maya‐Martinez, Roberto; Ayala, Isabel; Bougault, Catherine M.; Banzhaf, Manuel; Breukink, Eefjan; Vollmer, Waldemar; Simorre, Jean‐Pierre
• Is Part Of: Molecular microbiology. Volume 110:Issue 3(2018)
• Page Start: 335
• Page End: 356
• Publication Date: 2018-10-25
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14082
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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 polymerising (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. Abstract : The peptidoglycan cell wall synthesis activities of PBP1B are activated by binding of its regulator protein LpoB. This activation is achieved by binding‐induced conformational changes in PBP1B, which impact both of its catalytic domains. To ensure peptidoglycan synthesis is coordinated with outer membrane constriction during cell division, another regulatory protein CpoB binds to PBP1B and selectively modulates these conformational changes in response to Tol‐Pal function in the cell.