Skip to content
DraconiticResearch
Search Sources API
194,216 studies31 sourcesUpdated 53 min ago
Peer-reviewedCC BY-NC-NDNature communications

Structural basis of laminin mimicry by E. coli CNF1 and its therapeutic potential for cancer immunotherapy.

  • Yuyuan Zheng1
  • Yu Tang2
  • Mengzhen Wang1
  • Jie Zhang1
  • Jiangqing Chen2
  • Yuzhe Peng2
  • Xiaolin Shen2
  • Shize Zhang2
  • Lianqing Chen2
  • Yajun Guo1
  • Jie Sun3
  • Chun Zhou4
4 affiliations
  1. 1Department of Hematology and Cell Therapy of Sir Run Run Shaw Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
  2. 2Bone Marrow Transplantation Center of the First Affiliated Hospital, School of Basic Medical Science, Zhejiang University School of Medicine, Hangzhou, China.
  3. 3Bone Marrow Transplantation Center of the First Affiliated Hospital, School of Basic Medical Science, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  4. 4Department of Hematology and Cell Therapy of Sir Run Run Shaw Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
Read full textPDFDOICite

Abstract

The E. coli CNF1 toxin hijacks the host laminin 511 receptor, Lu/BCAM, to enter cells. Here, we present the high-resolution cryo-EM structures of full-length CNF1, the CNF1-BCAM complex, and the physiological laminin 511-BCAM complex. Structural analysis uncovers that CNF1 targets the V2 domain of BCAM, mimicking the interaction mode of laminin 511. We demonstrate that CNF1 binds BCAM with higher affinity than laminin 511, effectively displacing the physiological ligand from the cell surface. Leveraging this high-affinity interaction, we engineered a CNF1 D5-based T-cell engager (TCE). This TCE potently directs T cells to kill BCAM-overexpressing tumor cells in vitro and suppresses tumor progression in a metastatic ovarian cancer mouse model in female mice. These findings provide structural insight into how CNF1 hijacks the BCAM receptor and show how a pathogen-derived, high-affinity interaction can be harnessed to redirect T cells against BCAM-expressing tumors.

Related

  1. The cGAS–STING pathway in cancer immunotherapy: prognostic value and therapeutic potential
    Faizah A. Alabi, Sikiru Opeyemi Imodoye, Kamoru Ademola Adedokun +9
    Frontiers in ImmunologyPeer-reviewedCC BYFull text5 citedImmunologyOpenAlex
  2. Conserved mycobacteriophage protein uses structural mimicry to displace host initiation factors
    D. R. Parker, S. Ghosh, A. Dujiskova +9
    bioRxivPreprintCC BY-NC-NDFull textMicrobiologybioRxiv
  3. Dendritic cell diversity and dysfunction in cancer: implications for immunotherapy and therapeutic targeting
    Rong Wang, Yi Chen, Yan-fen Fang
    Acta Pharmacologica SinicaPeer-reviewedLicence not statedFull text2 citedImmunologyPMC
  4. Editorial: The differentiation and reprogramming of tumor-associated myeloid cells and therapeutic strategies for cancer immunotherapy
    Paul Takam Kamga, Lionel Franz Poulin, Li Lily Wang
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0Full textImmunologyCrossrefHAL
  5. In situ-activated engineered bacteria release combined dual-therapeutic proteins for tumor immunotherapy
    Xin-Ge Wang, Yue-Lan Huang, Xuan-Ren Shi +3
    iSciencePeer-reviewedCC BY 4.0ImmunologyMicrobiologyCell PressCrossref

Cite

BibTeXRIS
BibTeX
@article{zheng2026structural,
  title = {{Structural basis of laminin mimicry by E. coli CNF1 and its therapeutic potential for cancer immunotherapy.}},
  author = {Yuyuan Zheng and Yu Tang and Mengzhen Wang and Jie Zhang and Jiangqing Chen and Yuzhe Peng and Xiaolin Shen and Shize Zhang and Lianqing Chen and Yajun Guo and Jie Sun and Chun Zhou},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77975-2},
  url = {https://europepmc.org/article/MED/42907428},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Structural basis of laminin mimicry by E. coli CNF1 and its therapeutic potential for cancer immunotherapy.
AU  - Yuyuan Zheng
AU  - Yu Tang
AU  - Mengzhen Wang
AU  - Jie Zhang
AU  - Jiangqing Chen
AU  - Yuzhe Peng
AU  - Xiaolin Shen
AU  - Shize Zhang
AU  - Lianqing Chen
AU  - Yajun Guo
AU  - Jie Sun
AU  - Chun Zhou
PY  - 2026
DA  - 2026/09/22
JO  - Nature communications
DO  - 10.1038/s41467-026-77975-2
UR  - https://europepmc.org/article/MED/42907428
AB  - The E. coli CNF1 toxin hijacks the host laminin 511 receptor, Lu/BCAM, to enter cells. Here, we present the high-resolution cryo-EM structures of full-length CNF1, the CNF1-BCAM complex, and the physiological laminin 511-BCAM complex. Structural analysis uncovers that CNF1 targets the V2 domain of BCAM, mimicking the interaction mode of laminin 511. We demonstrate that CNF1 binds BCAM with higher affinity than laminin 511, effectively displacing the physiological ligand from the cell surface. Leveraging this high-affinity interaction, we engineered a CNF1 D5-based T-cell engager (TCE). This TCE potently directs T cells to kill BCAM-overexpressing tumor cells in vitro and suppresses tumor progression in a metastatic ovarian cancer mouse model in female mice. These findings provide structural insight into how CNF1 hijacks the BCAM receptor and show how a pathogen-derived, high-affinity interaction can be harnessed to redirect T cells against BCAM-expressing tumors.
SN  - 2041-1723
ER  -