The research paper titled Structure of an F-type phage tail-like bacteriocin from Listeria monocytogenes, co-authored by Dr. Ge Xiaofei, an assistant professor at the Faculty of Health and Wellness (FHW), City University of Macau (CityU), has been published in Nature Communications.
Nature Communications is a leading multidisciplinary open-access journal with an impact factor (IF) of 14.7. It is dedicated to publishing high-quality research across various fields, including biology, physics, chemistry, and earth sciences, focusing on significant breakthroughs in these areas.
This study presented the comprehensive structural analysis of monocin, an F-type phage tail-like bacteriocin produced by Listeria monocytogenes via the Cryo-electron microscopy (cryo-EM). It was the first to reveal the structural organization of this type of protein complex exhibiting bactericidal activity, providing crucial scientific evidence for understanding its bactericidal mechanism and a foundation for developing targeted bactericidal therapies.
The research team expressed 11 structural genes and two regulatory genes of monocin in Lactococcus lactis using genetic engineering. The cryo-EM imaging was captured to analyze its atomic structure of monocin. Although the overall structure exhibited high conformational flexibility, the team resolved the high-resolution 3D reconstructions of the proximal “cap domain,” distal “tip domain,” and “side fiber” using cryo-EM analyses. Based on rigid-body docking of the local structures and refinement, the molecular model of the entire monocin structure was constructed. The structural features suggested that monocin could achieve its biological functions through the synergy of modular structural domains.
The overall structure of monocin measured approximately 103 nm in length, consisting of 22 stacked hexameric rings of tail tube protein (TTP) FtbG, which formed a flexible tube connected by disulfide bonds between the adjacent FtbGs. At the proximal end, the tail tube was capped by a hexameric ring made of the terminator protein (TrP) FtbF. The distal end was sealed by trimers of the baseplate hub protein (BHP) FtbL, which also formed the spike. The side fibers were attached to the “fishing rod-treble hook” FtbN trimer formed by distal tail protein (DTP) FtbK.
In the side fibers, the FtbP trimer, each featuring a receptor-binding domain (RBD) at the distal end, could accurately identify the host cells. Another component of the side fibers, the FtbO trimer coordinated with ferric ions to enhance stability. Experiments indicated that truncating or removing FtbO did not impact the overall structural assembly of monocin, but it indeed disrupted its antibacterial activity, suggesting that FtbO might play an important role in the bactericidal process.
This study addressed the technical challenges posed by high conformational flexibility of molecular structures through cryo-EM reconstruction. It provided essential scientific insights into the bactericidal mechanism of monocin and established a foundation for developing targeted antibacterial therapies. Additionally, it filled a significant gap in the structural biology of phage tail-like bacteriocins.
Source: Faculty of Health and Wellness
