The PASTA domains of Bacillus subtilis PBP2B strengthen the interaction of PBP2B with DivIB

Angeles, Danae Morales; Macia-Valero, Alicia; Bohorquez, Laura C.; Scheffers, Dirk‐Jan

doi:10.1099/mic.0.000957

Cited by 11 publications

(9 citation statements)

References 43 publications

(67 reference statements)

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“…Furthermore, predicted DockQ values 32 for protein-protein interfaces with individual subunits ranged from 0.64 to 0.73 ( Table S3 ), indicating accurate predictions of protein complexes 26 . Finally, predictions for homologous complexes of FtsQLBWI in other diderm (gram negative) and monoderm (gram positive) species were largely similar, with notable differences at less conserved C-terminal domains, such as the different interactions reported for PASTA domains in FtsI homologs Bacillus subtilis Pbp2B 33 and Streptococcus pneumonia Pbp2X 34 ( Fig. S2B ).…”

Section: Resultsmentioning

confidence: 80%

Conformational changes in the essentialE. coliseptal cell wall synthesis complex suggest an activation mechanism

Britton

Yovanno

Costa

et al. 2022

Preprint

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The bacterial divisome, a macromolecular machine that is composed of more than thirty proteins in E. coli, orchestrates the essential process of cell wall constriction during cell division. Novel antimicrobial strategies can target protein-protein interactions within the divisome and will benefit from insights into divisome structure and dynamics. In this work, we combined structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis to construct a model of the core complex of the E. coli divisome composed of the essential septal cell wall synthase complex formed by FtsW and FtsI, and its regulators FtsQ, FtsL, FtsB, and FtsN. We observed extensive interactions in four key regions in the periplasmic domains of the complex. FtsQ, FtsL, and FtsB scaffold FtsI in an extended conformation with the FtsI transpeptidase domain lifted away from the membrane through interactions among the C-terminal domains. FtsN binds between FtsI and FtsL in a region rich in residues with superfission (activating) and dominant negative (inhibitory) mutations. Mutagenesis experiments in cellulo and in silico revealed that the essential domain of FtsN functions as a tether to tie FtsI and FtsL together, impacting interactions between the anchor-loop of FtsI and the putative catalytic region of FtsW, suggesting a mechanism of how FtsN activates the cell wall synthesis activities of FtsW and FtsI.

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Section: Resultsmentioning

confidence: 80%

Conformational changes in the essentialE. coliseptal cell wall synthesis complex suggest an activation mechanism

Britton

Yovanno

Costa

et al. 2022

Preprint

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“…S8A and B ) ( 14 , 35 ). Recently, the PASTA domains from B. subtilis PBP2B were shown to regulate PBP2B interaction with DivIB ( 51 ). S. aureus DivIB is a PG-binding protein essential for division, the depletion of which leads to septal plate formation loss ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division

Wacnik

Rao

Chen

et al. 2022

mBio

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Bacterial cell wall peptidoglycan is essential, and its synthesis is the target of clinically important antibiotics such as β-lactams. β-lactams target penicillin-binding proteins (PBPs) that assemble new peptidoglycan from its building blocks. The human pathogen Staphylococcus aureus only has two essential PBPs that can carry out all the functions necessary for growth and division.

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“…We did not observe an interaction between YneA and FtsW or YneA and FtsW‐L148P (Figure 6a,b). Since we did not detect a direct interaction between YneA and FtsW, we asked if YneA targets FtsW indirectly by interacting with other proteins involved in the late arriving divisome affecting cell division or peptidoglycan synthesis (Halbedel & Lewis, 2019; Kawai & Ogasawara, 2006; Król et al, 2012; Morales Angeles et al., 2020). First, we failed to observe an interaction between YneA and nine other proteins known to be involved in these processes (Figure 6a).…”

Section: Resultsmentioning

confidence: 99%

DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis

Masser

Burby

Hawkins

et al. 2021

Molecular Microbiology

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During normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS-induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA-induced checkpoint. We find that YneA C-terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA-enforced DNA damage checkpoint.With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.

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The PASTA domains of Bacillus subtilis PBP2B strengthen the interaction of PBP2B with DivIB

Cited by 11 publications

References 43 publications

Conformational changes in the essentialE. coliseptal cell wall synthesis complex suggest an activation mechanism

Conformational changes in the essentialE. coliseptal cell wall synthesis complex suggest an activation mechanism

Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division

DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis

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