![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
9MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
139MB |
| Item Type: | Article |
|---|---|
| Title: | Structural basis of Fusobacterium nucleatum adhesin Fap2 interaction with receptors on cancer and immune cells |
| Creators Name: | Schöpf, Felix, Marongiu, Gian L., Milaj, Klaudia, Sprink, Thiemo, Kikhney, Judith, Moter, Annette and Roderer, Daniel |
| Abstract: | Fusobacterium nucleatum is overrepresented in the colon microbiome of colorectal cancer patients and has been associated with tumor growth enhancement and metastasis. A pivotal pathogenic factor, the autotransporter adhesin Fap2, facilitates association to cancer and immune cells via the receptors Gal-GalNAc and TIGIT, respectively, leading to deactivation of immune cells. Mechanistic details of the Fap2/TIGIT interaction remain elusive as no structural data are available. Here, we report a system to recombinantly express functional Fap2 on the Escherichia coli surface, which interacts with Gal-GalNAc on cancer cells and with purified TIGIT with submicromolar affinity. Cryo-EM structures of Fap2, alone and in complex with TIGIT, show that the elongated ~50 nm long Fap2 extracellular region binds to TIGIT on its membrane-distal tip via an extension of a β-helix domain. Moreover, by combining structure predictions, cryo-EM, docking and molecular dynamics simulations, we identified a binding pit for Gal-GalNAc on the tip of Fap2. |
| Keywords: | Bacterial Adhesins, Colorectal Neoplasms, Cryoelectron Microscopy, Escherichia Coli, Fusobacterium Nucleatum, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 8104 |
| Date: | 29 August 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-63451-w |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
