9Y9W

Vibrio cholerae protein FrhA peptid-binding domain and adjacent split domain (S1127-F1439) in complex with peptide AGWTD X-ray crystallography structure

Summary for 9Y9W

• Entry DOI: 10.2210/pdb9y9w/pdb
• Related: 9Y9W
• Descriptor: Cadherin domain protein, Ala-Gly-Trp-Thr-Asp (AGWTD), CALCIUM ION, ... (6 entities in total)
• Functional Keywords: calcium, adhesin, rtx, peptide-binding domain, split domain, inhibitor, metal binding protein
• Biological source: Vibrio cholerae O395; More
• Total number of polymer chains: 12
• Total formula weight: 233503.44

Authors

Wang, M.,Guo, S.,Kinrade, B.,Davies, P. (deposition date: 2025-09-15, release date: 2025-12-03, Last modification date: 2026-03-25)

Primary citation

Wang, M.,Du, G.,Yongo-Luwawa, C.,Lu, A.,Kinrade, B.,Munro, K.,Klose, K.E.,Lubell, W.D.,Davies, P.,Guo, S.
Peptide-based ligand antagonists block a Vibrio cholerae adhesin.
Febs Lett., 600:631-643, 2026

PubMed Abstract: Vibrio cholerae, the causative agent of cholera, uses surface proteins such as the repeats-in-toxin (RTX) adhesin FrhA to colonize hosts and initiate infection. Blocking bacterial adhesion represents a promising therapeutic strategy to treat infections without promoting drug resistance. FrhA contains a peptide-binding domain (PBD) that is key for hemagglutination, human epithelial cell binding, and V. cholerae biofilm formation. Previous studies identified a lead pentapeptide ligand with the sequence Ala-Gly-Tyr-Thr-Asp (AGYTD) that blocks V. cholerae colonization of the mouse small intestine at high micromolar concentrations. In this study, a structure-guided approach identified a minimal D-amino acid-containing tripeptide motif with higher affinity for the FrhA-PBD and predicted metabolic stability. Our results contribute to the development of anti-adhesion strategies to combat infections. Impact statement Our study elucidates the molecular basis of peptide recognition by the Vibrio cholerae adhesin FrhA and develops minimal D-amino-acid peptides that block adhesion with nanomolar affinity. These findings advance understanding of RTX adhesins and provide a structural blueprint for next-generation anti-adhesion therapeutics against cholera and related infections.

PubMed: 41262002
DOI: 10.1002/1873-3468.70231

Experimental method

X-RAY DIFFRACTION (2.4 Å)