The mechanism of the phage-encoded protein antibiotic from ΦX174

• 成果类型: Article
• 署名作者: Orta, Anna K.; Riera, Nadia; Li, Yancheng E.; Tanaka, Shiho; Yun, Hyun Gi; Klaic, Lada; Clemons, William M., Jr.
• 署名单位: California Institute of Technology
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11498
• DOI: 10.1126/science.adg9091
• 发表日期: 2023-07-14
• 页码: 180-+
• 关键词: lysis protein; escherichia-coli; functional-characterization; enzymatic-activity; crystal-structure; prolyl isomerase; bacterial ghosts; host gene; mray; slyd

摘要

The historically important phage Phi X174 kills its host bacteria by encoding a 91-residue protein antibiotic called protein E. Using single-particle electron cryo-microscopy, we demonstrate that protein E bridges two bacterial proteins to form the transmembrane YES complex [MraY, protein E, sensitivity to lysis D (SlyD)]. Protein E inhibits peptidoglycan biosynthesis by obstructing the MraY active site leading to loss of lipid I production. We experimentally validate this result for two different viral species, providing a clear model for bacterial lysis and unifying previous experimental data. Additionally, we characterize the Escherichia coli MraY structure-revealing features of this essential enzyme-and the structure of the chaperone SlyD bound to a protein. Our structures provide insights into the mechanism of phage-mediated lysis and for structure-based design of phage therapeutics.