8F5D

Architecture of the MurE-MurF ligase bacterial cell wall biosynthesis complex

Summary for 8F5D

• Entry DOI: 10.2210/pdb8f5d/pdb
• Descriptor: Multifunctional fusion protein, SULFATE ION (3 entities in total)
• Functional Keywords: bacterial cell wall, antibiotic resistance, murs, complexes, ligase
• Biological source: Bordetella pertussis 18323
• Total number of polymer chains: 1
• Total formula weight: 85206.64

Authors

Shirakawa, K.T.,Sala, F.A.,Miyachiro, M.M.,Job, V.,Trindade, D.M.,Dessen, A. (deposition date: 2022-11-14, release date: 2023-06-07, Last modification date: 2024-04-03)

Primary citation

Shirakawa, K.T.,Sala, F.A.,Miyachiro, M.M.,Job, V.,Trindade, D.M.,Dessen, A.
Architecture and genomic arrangement of the MurE-MurF bacterial cell wall biosynthesis complex.
Proc.Natl.Acad.Sci.USA, 120:e2219540120-e2219540120, 2023

PubMed 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, genes are present in a single operon within the well conserved cluster, and in some cases, pairs of 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 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 Ks 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.

PubMed: 37186837
DOI: 10.1073/pnas.2219540120

Experimental method

X-RAY DIFFRACTION (2.56 Å)