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-Structure paper
タイトル | Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 6119, Year 2022 |
掲載日 | 2022年10月17日 |
著者 | Akihiro Kawamoto / Tomohito Yamada / Toru Yoshida / Yusui Sato / Takayuki Kato / Hideaki Tsuge / |
PubMed 要旨 | Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically ...Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets. CDTb has been proposed to be a di-heptamer, but its physiological heptameric structure has not yet been reported. Here, we report the cryo-EM structure of CDTa bound to the CDTb-pore, which reveals that CDTa binding induces partial unfolding and tilting of the first CDTa α-helix. In the CDTb-pore, an NSS-loop exists in 'in' and 'out' conformations, suggesting its involvement in substrate translocation. Finally, 3D variability analysis revealed CDTa movements from a folded to an unfolded state. These dynamic structural information provide insights into drug design against hypervirulent C. difficile strains. |
リンク | Nat Commun / PubMed:36253419 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.56 - 3.19 Å |
構造データ | EMDB-32041, PDB-7vnj: EMDB-32043, PDB-7vnn: EMDB-33188: Complex map of Clostridioides difficile enzymatic component (CDTa) and binding component (CDTb) di-heptamer EMDB-34136, PDB-7yvq: EMDB-34137, PDB-7yvs: |
化合物 | ChemComp-CA: |
由来 |
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キーワード | TOXIN / Complex / Translocation / Oligomer / Unfoldase |