ジャーナル: Nature / 年: 2014 タイトル: Mechanism of Tc toxin action revealed in molecular detail. 著者: Dominic Meusch / Christos Gatsogiannis / Rouslan G Efremov / Alexander E Lang / Oliver Hofnagel / Ingrid R Vetter / Klaus Aktories / Stefan Raunser / 要旨: Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly ...Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. Here we report the first, to our knowledge, high-resolution structures of a TcA subunit in its prepore and pore state and of a complete 1.7 megadalton Tc complex. The structures reveal that, in addition to a translocation channel, TcA forms four receptor-binding sites and a neuraminidase-like region, which are important for its host specificity. pH-induced opening of the shell releases an entropic spring that drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to TcA opens a gate formed by a six-bladed β-propeller and results in a continuous protein translocation channel, whose architecture and properties suggest a novel mode of protein unfolding and translocation. Our results allow us to understand key steps of infections involving Tc toxins at the molecular level.
Partial-symmetry projection matching approach (after each refinement round, C5 symmetry was applied for the TcdA1 component).
CTF補正
詳細: Each particle
最終 再構成
想定した対称性 - 点群: C1 (非対称) / アルゴリズム: OTHER / 解像度のタイプ: BY AUTHOR / 解像度: 9.0 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: Sparx 詳細: TcdA1 component of the complex has an average resolution of 7.4 A, whereas the TcdB2/TccC3 components an average resolution of 11 A. Local resolution calculations were performed using a 20 A ...詳細: TcdA1 component of the complex has an average resolution of 7.4 A, whereas the TcdB2/TccC3 components an average resolution of 11 A. Local resolution calculations were performed using a 20 A sphere for windowed-FSC calculations at 0.5. 使用した粒子像数: 43000