Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD <subscript>7</subscript> .
In: Cell reports, Jg. 43 (2024-02-27), Heft 2, S. 113727
Online
academicJournal
Zugriff:
The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD 1,2,7 , are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible for pathogenesis associated with Clostridioides difficile infection. We employ a live-cell assay examining the affinity between full-length FZDs and TcdB. Moreover, we present cryoelectron microscopy structures of TcdB alone and in complex with full-length FZD 7 , which reveal that large structural rearrangements of the combined repetitive polypeptide domain are required for interaction with FZDs and other TcdB receptors, constituting a first step for receptor recognition. Furthermore, we show that bezlotoxumab, an FDA-approved monoclonal antibody to treat Clostridioides difficile infection, favors the apo-TcdB structure and thus disrupts binding with FZD 7 . The dynamic transition between the two conformations of TcdB also governs the stability of the pore-forming region. Thus, our work provides structural and functional insight into how conformational dynamics of TcdB determine receptor binding.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Titel: |
Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD <subscript>7</subscript> .
|
---|---|
Autor/in / Beteiligte Person: | Kinsolving, J ; Bous, J ; Kozielewicz, P ; Košenina, S ; Shekhani, R ; Grätz, L ; Masuyer, G ; Wang, Y ; Stenmark, P ; Dong, M ; Schulte, G |
Link: | |
Zeitschrift: | Cell reports, Jg. 43 (2024-02-27), Heft 2, S. 113727 |
Veröffentlichung: | [Cambridge, MA] : Cell Press, c 2012-, 2024 |
Medientyp: | academicJournal |
ISSN: | 2211-1247 (electronic) |
DOI: | 10.1016/j.celrep.2024.113727 |
Schlagwort: |
|
Sonstiges: |
|