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-Structure paper
タイトル | Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD. |
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ジャーナル・号・ページ | Cell Rep, Vol. 43, Issue 2, Page 113727, Year 2024 |
掲載日 | 2024年2月27日 |
著者 | Julia Kinsolving / Julien Bous / Pawel Kozielewicz / Sara Košenina / Rawan Shekhani / Lukas Grätz / Geoffrey Masuyer / Yuankai Wang / Pål Stenmark / Min Dong / Gunnar Schulte / |
PubMed 要旨 | The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible ...The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, 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, 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. 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. |
リンク | Cell Rep / PubMed:38308843 |
手法 | EM (単粒子) |
解像度 | 2.89 - 3.63 Å |
構造データ | EMDB-18373, PDB-8qen: EMDB-18374, PDB-8qeo: EMDB-18402: cryo-EM structure of apo-TcdB EMDB-18403: cryo-EM map of apo Clostridioides difficile toxin B EMDB-18409: cryo-EM structure of TcdB-FZD7 EMDB-18410: cryo-EM structure of TcdB-FZD7 EMDB-18411: cryo-EM structure of TcdB-FZD7 |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | TOXIN / microbiology / pore forming region / CROP dynamics / Structural Genomics / Structural Genomics Consortium / SGC / micriobiology / class F G protein-coupled receptors |