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Architecture and genomic arrangement of the MurE-MurF bacterial cell wall biosynthesis complex.


ABSTRACT: Peptidoglycan (PG) is a central component of the bacterial cell wall, and the disruption of its biosynthetic pathway has been a successful antibacterial strategy for decades. PG biosynthesis is initiated in the cytoplasm through sequential reactions catalyzed by Mur enzymes that have been suggested to associate into a multimembered complex. This idea is supported by the observation that in many eubacteria, mur genes are present in a single operon within the well conserved dcw cluster, and in some cases, pairs of mur genes are fused to encode a single, chimeric polypeptide. We performed a vast genomic analysis using >140 bacterial genomes and mapped Mur chimeras in numerous phyla, with Proteobacteria carrying the highest number. MurE-MurF, the most prevalent chimera, exists in forms that are either directly associated or separated by a linker. The crystal structure of the MurE-MurF chimera from Bordetella pertussis reveals a head-to-tail, elongated architecture supported by an interconnecting hydrophobic patch that stabilizes the positions of the two proteins. Fluorescence polarization assays reveal that MurE-MurF interacts with other Mur ligases via its central domains with KDs in the high nanomolar range, backing the existence of a Mur complex in the cytoplasm. These data support the idea of stronger evolutionary constraints on gene order when encoded proteins are intended for association, establish a link between Mur ligase interaction, complex assembly and genome evolution, and shed light on regulatory mechanisms of protein expression and stability in pathways of critical importance for bacterial survival.

SUBMITTER: Shirakawa KT 

PROVIDER: S-EPMC10214165 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Architecture and genomic arrangement of the MurE-MurF bacterial cell wall biosynthesis complex.

Shirakawa Karina T KT   Sala Fernanda Angélica FA   Miyachiro Mayara M MM   Job Viviana V   Trindade Daniel Maragno DM   Dessen Andréa A  

Proceedings of the National Academy of Sciences of the United States of America 20230515 21


Peptidoglycan (PG) is a central component of the bacterial cell wall, and the disruption of its biosynthetic pathway has been a successful antibacterial strategy for decades. PG biosynthesis is initiated in the cytoplasm through sequential reactions catalyzed by Mur enzymes that have been suggested to associate into a multimembered complex. This idea is supported by the observation that in many eubacteria, <i>mur</i> genes are present in a single operon within the well conserved <i>dcw</i> clust  ...[more]

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