8WEO

Bacteroides fragilis toxin in complex with neutralization nanobody

Summary for 8WEO

• Entry DOI: 10.2210/pdb8weo/pdb
• Descriptor: Fragilysin, NB243, ZINC ION, ... (4 entities in total)
• Functional Keywords: bacteroides fragilis toxin, bft, nanobody, toxin/immune system, toxin-immune system complex
• Biological source: Bacteroides fragilis; More
• Total number of polymer chains: 4
• Total formula weight: 69555.44

Authors

Guo, Y.,Wen, Y. (deposition date: 2023-09-18, release date: 2024-09-25, Last modification date: 2026-04-08)

Primary citation

Guo, Y.,Ouyang, Z.,He, W.,Qin, Q.,Zhang, J.,Yu, T.,Jiao, M.,Hwang, P.M.,Zheng, F.,Muyldermans, S.,Wen, Y.
Mechanistic diversity of Bacteroides fragilis toxins and neutralization with single domain antibody.
Cell Chem Biol, 33:102-116.e6, 2026

PubMed Abstract: Enterotoxigenic Bacteroides fragilis (ETBF) promotes colonic inflammation by secreting metalloenzyme toxins (BFTs). Understanding BFT mechanisms and developing neutralization strategies is critical. Here, we have solved the structures of BFT-1 and BFT-2, revealing that residue 357 in the active site of the catalytic domain explains the diversity of function observed in BFT subtypes. We demonstrate that BFTs can directly cleave human epithelial-cadherin at extracellular domain 4, with BFT-2 possessing the highest activity. Using an alpaca antibody library, we identified a single-domain antibody, Nb2.43, targeting the BFTs. Nb2.43 can neutralize all three subtypes of BFT by directly binding the metalloenzyme catalytic zinc ion with its CDR3 antigen-binding loop. Furthermore, Nb2.43 blocks cleavage of E-cadherin by BFT and prevents the damage caused by ETBF in vitro and in a mouse colitis model. This work provides structural insights into BFT diversity and delivers a therapeutic nanobody against ETBF-mediated inflammation.

PubMed: 41544614
DOI: 10.1016/j.chembiol.2025.12.009

Experimental method

X-RAY DIFFRACTION (1.5 Å)