9U94

Cryo-EM structure of Fusobacterium nucleatum CbpF in complex with human CEACAM1

Summary for 9U94

• Entry DOI: 10.2210/pdb9u94/pdb
• EMDB information: 63959
• Descriptor: Fusobacterium nucleatum CbpF, Cell adhesion molecule CEACAM1 (2 entities in total)
• Functional Keywords: fusobacterium nucleatum, trimeric autotransporter adhesin, cbpf, ceacam1, cell adhesion
• Biological source: Fusobacterium nucleatum; More
• Total number of polymer chains: 6
• Total formula weight: 155363.99

Authors

Li, L.J.,Shen, F.,Zhao, X.,Gao, G.F. (deposition date: 2025-03-27, release date: 2025-09-03, Last modification date: 2026-03-18)

Primary citation

Shen, F.,Li, L.,Yang, D.,Tang, Z.,Zhang, L.,Liu, K.,Hou, W.,Lu, Z.,Fang, J.Y.,Qi, J.,Zhao, X.,Gao, G.F.
Binding of Fusobacterium nucleatum autotransporter adhesin CbpF to human CEACAM1 and CEACAM5: A Velcro model for bacterium adhesion.
Proc.Natl.Acad.Sci.USA, 122:e2516574122-e2516574122, 2025

PubMed Abstract: In eukaryotic systems, three major types of cell junctions have been well characterized. While bacterial adhesion mechanisms also exhibit remarkable diversity, the molecular processes that regulate the dynamic modulation of binding strength between elongated bacterial cells and host cells remain poorly understood. () utilizes the surface adhesin CbpF to interact with the highly expressed host receptors CEACAM1 and CEACAM5 on cancer cells to facilitate tumor colonization. By elucidating the structural details of CbpF binding to human CEACAM1/CEACAM5 receptors, and through mechanistic investigations, we identified that the prominent EFNGQYQ loop on CbpF and the key Q78 residue of CEACAM1/CEACAM5 constitute the molecular linchpin of this pathogen-host interface. Furthermore, we found a distinct type of binding particle and proposed a Velcro-like adhesion model. In this model, CbpF mediates robust attachment through the simultaneous interaction of multiple binding sites, akin to the interlocking mechanism of Velcro. This multivalent interaction allows to dynamically switch between firm anchoring and easy detachment, adapting to varying physiological microenvironments. Our study elucidates the dynamic modulation of bacterial adhesion strength and lays the foundation for developing therapeutic interventions to disrupt the bacterium-host interface.

PubMed: 40928870
DOI: 10.1073/pnas.2516574122

Experimental method

ELECTRON MICROSCOPY (2.11 Å)