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| Title | Atomic structures of a bacteriocin targeting Gram-positive bacteria. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 7057, Year 2024 |
| Publish date | Aug 16, 2024 |
 Authors | Xiaoying Cai / Yao He / Iris Yu / Anthony Imani / Dean Scholl / Jeff F Miller / Z Hong Zhou /  |
| 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; ...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. |
 External links | Nat Commun / PubMed:39152109 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.2 - 6.1 Å |
| Structure data | EMDB-42953, PDB-8v3t: EMDB-42956, PDB-8v3w:  EMDB-42957: CryoEM Structure of Diffocin - precontracted - Baseplate reconstructed in C6 symmetry  EMDB-42958: CryoEM Structure of Diffocin - precontracted - Baseplate reconstructed in C3 symmetry EMDB-42959, PDB-8v3x: EMDB-42960, PDB-8v3y: EMDB-42961, PDB-8v3z: EMDB-42962, PDB-8v40: EMDB-42963, PDB-8v41: EMDB-42964, PDB-8v43: |
| Source |
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 Keywords | VIRUS LIKE PARTICLE / Phage tail-like / bacteriocin / collar / pre-contraction / baseplate / trunk / post-contraction |
clostridioides difficile (bacteria)