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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

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

Résumé

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 K D s 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.
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Dates et versions

hal-04162887 , version 1 (15-11-2023)

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Karina Shirakawa, Fernanda Angélica Sala, Mayara Miyachiro, Viviana Job, Daniel Maragno Trindade, et al.. Architecture and genomic arrangement of the MurE–MurF bacterial cell wall biosynthesis complex. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (21), pp.e2219540120. ⟨10.1073/pnas.2219540120⟩. ⟨hal-04162887⟩
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