8V3X

CryoEM Structure of Diffocin - precontracted - Trunk

Summary for 8V3X

• Entry DOI: 10.2210/pdb8v3x/pdb
• EMDB information: 42959
• Descriptor: Sheath (CD1363), Tube (CD1364) (2 entities in total)
• Functional Keywords: phage tail-like, bacteriocin, trunk, pre-contraction, virus like particle
• Biological source: Clostridioides difficile; More
• Total number of polymer chains: 42
• Total formula weight: 1091512.21

Authors

Cai, X.Y.,He, Y.,Zhou, Z.H. (deposition date: 2023-11-28, release date: 2024-08-28)

Primary citation

Cai, X.,He, Y.,Yu, I.,Imani, A.,Scholl, D.,Miller, J.F.,Zhou, Z.H.
Atomic structures of a bacteriocin targeting Gram-positive bacteria.
Nat Commun, 15:7057-7057, 2024

PubMed Abstract: Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.

PubMed: 39152109
DOI: 10.1038/s41467-024-51038-w

Experimental method

ELECTRON MICROSCOPY (2.2 Å)