9QE7

Membrane-distal part of extracellular domain of the Fap2 autotransporter adhesin from Fusobacterium nucleatum ATCC23726

Summary for 9QE7

• Entry DOI: 10.2210/pdb9qe7/pdb
• EMDB information: 53049
• Descriptor: Outer membrane autotransporter barrel domain protein (1 entity in total)
• Functional Keywords: type v secretion system, autotransporter, colorectal cancer, bacterial adhesion, cell adhesion
• Biological source: Fusobacterium nucleatum
• Total number of polymer chains: 1
• Total formula weight: 340269.38

Authors

Schoepf, F.,Marongiu, G.L.,Milaj, K.,Sprink, T.,Kikhney, J.,Moter, A.,Roderer, D. (deposition date: 2025-03-07, release date: 2025-07-30, Last modification date: 2025-09-10)

Primary citation

Schopf, F.,Marongiu, G.L.,Milaj, K.,Sprink, T.,Kikhney, J.,Moter, A.,Roderer, D.
Structural basis of Fusobacterium nucleatum adhesin Fap2 interaction with receptors on cancer and immune cells.
Nat Commun, 16:8104-8104, 2025

PubMed 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.

PubMed: 40883327
DOI: 10.1038/s41467-025-63451-w

Experimental method

ELECTRON MICROSCOPY (4.4 Å)