8F5D

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

8F5D の概要

• エントリーDOI: 10.2210/pdb8f5d/pdb
• 分子名称: Multifunctional fusion protein, SULFATE ION (3 entities in total)
• 機能のキーワード: bacterial cell wall, antibiotic resistance, murs, complexes, ligase
• 由来する生物種: Bordetella pertussis 18323
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 85206.64

構造登録者

Shirakawa, K.T.,Sala, F.A.,Miyachiro, M.M.,Job, V.,Trindade, D.M.,Dessen, A. (登録日: 2022-11-14, 公開日: 2023-06-07, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.56 Å)