Binding of Fusobacterium nucleatum autotransporter adhesin CbpF to human CEACAM1 and CEACAM5: A Velcro model for bacterium adhesion

• 成果类型: Article
• 署名作者: Shen, Fan; Li, Linjie; Yang, Dongchun; Tang, Zhexiao; Zhang, Lu; Liu, Kefang; Hou, Wenzhe; Lu, Zhuozhuang; Fang, Jing - Yuan; Qi, Jianxun; Zhao, Xin; Gao, George F.
• 署名单位: Chinese Academy of Sciences; Institute of Microbiology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Institute of Process Engineering, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Shanghai Jiao Tong University; Chinese Center for Disease Control & Prevention; National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control & Prevention
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14247
• DOI: 10.1073/pnas.2516574122
• 发表日期: 2025-09-16
• 关键词: particle cryo-em; domain; protein; cancer; molecules; target; entry

摘要

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. Fusobacterium nucleatum (F. nucleatum) 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 F. nucleatum 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 interventions to the bacterium-host interface.