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| Title | Stepwise firing mechanism of an extracellular contractile injection system. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2026 |
| Publish date | Apr 24, 2026 |
 Authors | Jingwei Xu / Charles F Ericson / Elena R Toenshoff / Martin Pilhofer /   |
| PubMed Abstract | Contractile injection systems (CISs) mediate cell-cell interactions and are widespread among bacteria and archaea. These phage tail-like macromolecular machines puncture their target by a tube that ...Contractile injection systems (CISs) mediate cell-cell interactions and are widespread among bacteria and archaea. These phage tail-like macromolecular machines puncture their target by a tube that is propelled by a contractile sheath. The mechanism underlying CIS firing, which starts with target binding and ends with sheath contraction, remains unclear. Here, we investigate the extracellular CIS from Algoriphagus machipongonensis (AlgoCIS) by a multimodal cryo-electron microscopy approach and structure-guided engineering, which allowed us to arrest AlgoCIS in multiple intermediate states of firing. Together with the post-firing structure, our data suggest a stepwise firing mechanism involving all structural modules: signal propagation starts with the binding of the tail-fibers, followed by opening of the cage, an expansion of the baseplate iris, and resulting in sheath contraction and the release of cap adaptor. Our study will serve as a framework for understanding the firing mechanism of diverse CISs and will facilitate the engineering of CISs for biomedical applications. |
 External links | Nat Commun / PubMed:42031783 |
| Methods | EM (single particle) / EM (subtomogram averaging) / EM (tomography) |
| Resolution | 3.2 - 60.0 Å |
| Structure data | EMDB-66211, PDB-9wsz: EMDB-66212, PDB-9wt0: EMDB-66213, PDB-9wt1:  EMDB-66214: CryoEM structure of the proximal sheath layer connected to the baseplate wedge in the contracted AlgoCIS  EMDB-69920: CryoEM structure of the baseplate iris in the post-firing AlgoCIS upon low-pH treatment  EMDB-69921: CryoEM structure of the baseplate iris in the pre-firing non-contractile AlgoCIS upon low-pH treatment  EMDB-69922: CryoEM structure of the baseplate iris with partial open cage in the non-contractile AlgoCIS upon low-pH treatment  EMDB-69923: Sub-tomogram average of pre-firing AlgoCIS on the E. pacifica surface.  EMDB-69925: Cryo-tomogram of purified AlgoCIS incubated with E. pacifica. |
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 Keywords | STRUCTURAL PROTEIN / Contractile injection system / CryoEM / marine bacterium |
algoriphagus machipongonensis (bacteria)