Phosphorylation-dependent activation of the cell wall synthase PBP2a in Streptococcus pneumoniae by MacP

Proceedings of the National Academy of Sciences of the United States of America
Andrew K FentonDavid Z Rudner

Abstract

Most bacterial cells are surrounded by an essential cell wall composed of the net-like heteropolymer peptidoglycan (PG). Growth and division of bacteria are intimately linked to the expansion of the PG meshwork and the construction of a cell wall septum that separates the nascent daughter cells. Class A penicillin-binding proteins (aPBPs) are a major family of PG synthases that build the wall matrix. Given their central role in cell wall assembly and importance as drug targets, surprisingly little is known about how the activity of aPBPs is controlled to properly coordinate cell growth and division. Here, we report the identification of MacP (SPD_0876) as a membrane-anchored cofactor of PBP2a, an aPBP synthase of the Gram-positive pathogen Streptococcus pneumoniae We show that MacP localizes to the division site of S. pneumoniae, forms a complex with PBP2a, and is required for the in vivo activity of the synthase. Importantly, MacP was also found to be a substrate for the kinase StkP, a global cell cycle regulator. Although StkP has been implicated in controlling the balance between the elongation and septation modes of cell wall synthesis, none of its substrates are known to modulate PG synthetic activity. Here we show that a ...Continue Reading

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Citations

Sep 20, 2018·Médecine sciences : M/S·Sylvie ManuseChristophe Grangeasse
Aug 5, 2020·Microbiology·Danae Morales AngelesDirk-Jan Scheffers
Sep 6, 2019·Nature Reviews. Microbiology·Boris MacekIvan Mijakovic
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Daniel StraumeLeiv Sigve Håvarstein
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Apr 28, 2020·FEBS Letters·Julie Bonne KøhlerIvan Mijakovic
Feb 16, 2021·Current Opinion in Microbiology·Adrien Ducret, Christophe Grangeasse
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Feb 10, 2021·Journal of Bacteriology·Anja Ruud WintherDaniel Straume
May 1, 2021·Genome Biology·Carolin M KobrasSamuel K Sheppard
Jun 8, 2019·Microbiology Spectrum·Waldemar VollmerAlexander Tomasz
Aug 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Marios F SardisThomas G Bernhardt
Aug 20, 2021·Molecular Microbiology·Jordan DelisleThierry Doan

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