Large-scale structural changes accompany binding of lethal factor to anthrax protective antigen: a cryo-electron microscopic study.
Large-scale structural changes accompany binding of lethal factor to anthrax protective antigen: a cryo-electron microscopic study.
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大规模结构变化伴随着致死因子与炭疽保护性抗原的结合：一项冷冻电子显微镜研究。
DOI：
10.1016/j.str.2004.09.010
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Mitra,AlokK
中科院分区：
文献类型：
--
作者：
Ren,Gang;Quispe,Joel;Leppla,StephenH;Mitra,AlokK
炭疽毒素（Anthrax toxin，AT）是由炭疽芽孢杆菌（Bacillus anthracis）分泌的一种由致死因子（LF，90 kDa）、水肿因子（EF，89 kDa）和保护性抗原（PA，83 kDa）组成的三蛋白混合物。炭疽毒性的步骤包括：（1）配体（EF/LF）与PA的N-末端蛋白水解裂解后产生的PA 63七聚体（PA 63 h）结合，（2）复合物内吞后，配体通过一种未知的机制易位到胞质溶胶中。通过冷冻电子显微镜对悬浮在玻璃化缓冲液中的标本的图像进行分析，直接观察到PA 63 h. LF复合物，这表明LF分子定位于低聚物的非膜相互作用面，与四个连续的PA 63单体相互作用，并部分解开七聚体，从而扩大了中央管腔。在PA 63 h中观察到的结构重组可能有助于大的90 kDa LF分子通过管腔，最终递送穿过膜双层。
Anthrax toxin (AT), secreted byBacillus anthracis, is a three-protein cocktail of lethal factor (LF, 90 kDa), edema factor (EF, 89 kDa), and the protective antigen (PA, 83 kDa). Steps in anthrax toxicity involve (1) binding of ligand (EF/LF) to a heptamer of PA63 (PA63h) generated after N-terminal proteolytic cleavage of PA and, (2) following endocytosis of the complex, translocation of the ligand into the cytosol by an as yet unknown mechanism. The PA63h.LF complex was directly visualized from analysis of images of specimens suspended in vitrified buffer by cryo-electron microscopy, which revealed that the LF molecule, localized to the nonmembrane-interacting face of the oligomer, interacts with four successive PA63 monomers and partially unravels the heptamer, thereby widening the central lumen. The observed structural reorganization in PA63h likely facilitates the passage of the large 90 kDa LF molecule through the lumen en route to its eventual delivery across the membrane bilayer.