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| Title | Function and firing of the contractile injection system requires the membrane protein CisA. |
|---|---|
| Journal, issue, pages | Elife, Vol. 14, Year 2025 |
| Publish date | Jul 8, 2025 |
 Authors | Bastien Casu / Joseph W Sallmen / Peter E Haas / Govind Chandra / Pavel Afanasyev / Jingwei Xu / Martin Pilhofer / Susan Schlimpert /   |
| PubMed Abstract | Bacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from (CIS) are ...Bacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from (CIS) are localized in the cytoplasm. Under stress, they induce cell death and impact the life cycle. It remains unknown, however, whether CIS require accessory proteins to directly interact with the cytoplasmic membrane to function. Here, we characterize the putative membrane adaptor CisA, a conserved factor in CIS gene clusters across species. We show by cryo-electron tomography imaging and in vivo assays that CIS contraction and function depend on CisA. Using single-particle cryo-electron microscopy, we provide an atomic model of the extended CIS apparatus; however, CisA is not part of the complex. Instead, our findings show that CisA is a membrane protein with a cytoplasmic N-terminus predicted to interact with CIS components, thereby providing a possible mechanism for mediating CIS recruitment to the membrane and subsequent firing. Our work shows that CIS function in multicellular bacteria is distinct from type VI secretion systems and extracellular CIS, and possibly evolved due to the role CIS play in regulated cell death. |
 External links | Elife / PubMed:40626860 / PubMed Central |
| Methods | EM (tomography) / EM (single particle) |
| Resolution | 3.4 - 3.8 Å |
| Structure data |  EMDB-50935: Cryo electron tomogram of Streptomyces coelicolor - ScoDelta4242 membrane protein CisA mutant - Intact hyphae  EMDB-50939: Cryo electron tomogram of Streptomyces coelicolor - ScoDelta4242 membrane protein CisA mutant - Ghost cells  EMDB-50940: Cryo electron tomogram of Streptomyces coelicolor - ScoDelta4242 complemented membrane protein CisA strain - Intact hyphae  EMDB-50944: Cryo electron tomogram of Streptomyces coelicolor - ScoDelta4242 complemented membrane protein CisA strain - Ghost cells  EMDB-50948: Cryo electron tomogram of Streptomyces coelicolor - Intact hyphae  EMDB-50949: Cryo electron tomogram of Streptomyces coelicolor - Ghost cells EMDB-51564, PDB-9gtp: EMDB-51565, PDB-9gtr: EMDB-51566, PDB-9gts: |
| Source |
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 Keywords | STRUCTURAL PROTEIN / Contractile injection system |
streptomyces coelicolor a3(2) (bacteria)
