4W6Y

Co-complex structure of the lectin domain of F18 fimbrial adhesin FedF with inhibitory nanobody NbFedF9

Summary for 4W6Y

• Entry DOI: 10.2210/pdb4w6y/pdb
• Related: 4B4P 4W6W 4W6X
• Descriptor: F18 fimbrial adhesin AC, Nanobody NbFedF9, SULFATE ION, ... (4 entities in total)
• Functional Keywords: adhesin, fimbriae, cell adhesion, inhibitor
• Biological source: Escherichia coli DH5[alpha]; More
• Total number of polymer chains: 2
• Total formula weight: 31584.69

Authors

Moonens, K.,De Kerpel, M.,Coddens, A.,Cox, E.,Pardon, E.,Remaut, H.,De Greve, H. (deposition date: 2014-08-21, release date: 2014-12-17, Last modification date: 2024-10-23)

Primary citation

Moonens, K.,De Kerpel, M.,Coddens, A.,Cox, E.,Pardon, E.,Remaut, H.,De Greve, H.
Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli.
Plos One, 9:e114691-e114691, 2014

PubMed Abstract: Post-weaning diarrhea and edema disease caused by F18 fimbriated E. coli are important diseases in newly weaned piglets and lead to severe production losses in farming industry. Protective treatments against these infections have thus far limited efficacy. In this study we generated nanobodies directed against the lectin domain of the F18 fimbrial adhesin FedF and showed in an in vitro adherence assay that four unique nanobodies inhibit the attachment of F18 fimbriated E. coli bacteria to piglet enterocytes. Crystallization of the FedF lectin domain with the most potent inhibitory nanobodies revealed their mechanism of action. These either competed with the binding of the blood group antigen receptor on the FedF surface or induced a conformational change in which the CDR3 region of the nanobody displaces the D″-E loop adjacent to the binding site. This D″-E loop was previously shown to be required for the interaction between F18 fimbriated bacteria and blood group antigen receptors in a membrane context. This work demonstrates the feasibility of inhibiting the attachment of fimbriated pathogens by employing nanobodies directed against the adhesin domain.

PubMed: 25502211
DOI: 10.1371/journal.pone.0114691

Experimental method

X-RAY DIFFRACTION (1.57 Å)