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-Structure paper
| タイトル | Structural basis of Fusobacterium nucleatum adhesin Fap2 interaction with receptors on cancer and immune cells. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 8104, Year 2025 |
| 掲載日 | 2025年8月29日 |
著者 | Felix Schöpf / Gian L Marongiu / Klaudia Milaj / Thiemo Sprink / Judith Kikhney / Annette Moter / Daniel Roderer / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:40883327 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.4 - 6.0 Å |
| 構造データ | ![]() EMDB-53048: Extracellular domain of the Fap2 autotransporter adhesin from Fusobacterium nucleatum ATCC23726 EMDB-53049, PDB-9qe7: ![]() EMDB-53052: Complex of Fap2 from Fusobacterium nucleatum with human TIGIT |
| 由来 |
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キーワード | CELL ADHESION / Type V secretion system / autotransporter / colorectal cancer / bacterial adhesion |
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fusobacterium nucleatum (バクテリア)
Homo sapiens (ヒト)
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