Structure and activity of the septal peptidoglycan hydrolysis machinery crucial for bacterial cell division

• Published in: PLoS biology Vol. 22; no. 5; p. e3002628
• Main Authors: Chen, Yatian, Gu, Jiayue, Yang, Biao, Yang, Lili, Pang, Jie, Luo, Qinghua, Li, Yirong, Li, Danyang, Deng, Zixin, Dong, Changjiang, Dong, Haohao, Zhang, Zhengyu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.05.2024; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphate - metabolism; Amidase; Antibiotics; ATP; ATP-Binding Cassette Transporters; Bacteria; Bacterial cell walls; Bacterial Outer Membrane Proteins; Biology and Life Sciences; Cell Cycle Proteins; Cell Division; Cell Wall - metabolism; Cell walls; Conformation; Critical components; Cryoelectron Microscopy; Cystic Fibrosis Transmembrane Conductance Regulator; Degradation; Drug development; Drug resistance; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gram-negative bacteria; Gram-positive bacteria; Hydrolysis; Lipoproteins; Medicine and Health Sciences; Microbiological research; Models, Molecular; N-Acetylmuramoyl-L-alanine Amidase - genetics; N-Acetylmuramoyl-L-alanine Amidase - metabolism; Peptidoglycan - metabolism; Peptidoglycans; Physical Sciences; Physiological aspects; Protein Conformation; Proteins; Research and Analysis Methods; Structure; China
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3002628

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.