Microtubule-severing enzymes katanin, spastin and fidgetin are AAA ATPases important for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. Because of a lack of known 3D structures for these enzymes, their mechanism of action has remained poorly understood. Here we report the X-ray crystal structure of the monomeric AAA katanin module from Caenorhabditis elegans and cryo-EM reconstructions of the hexamer in two conformations. The structures reveal an unexpected asymmetric arrangement of the AAA domains mediated by structural elements unique to microtubule-severing enzymes and critical for their function. The reconstructions show that katanin cycles between open spiral and closed ring conformations, depending on the ATP occupancy of a gating protomer that tenses or relaxes interprotomer interfaces. Cycling of the hexamer between these conformations would provide the power stroke for microtubule severing.

中文翻译：

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Katanin 螺旋和环形结构揭示了微管切断的动力冲程

微管切断酶 katanin、spastin 和 fidgetin 是 AAA ATP 酶，对于轴突、纺锤体和纤毛中复杂微管阵列的生物发生和维持很重要。由于缺乏这些酶的已知 3D 结构，它们的作用机制仍然知之甚少。在这里，我们报告了来自秀丽隐杆线虫的单体 AAA katanin 模块的 X 射线晶体结构和两种构象的六聚体的冷冻电镜重建。这些结构揭示了由微管切断酶特有的结构元素介导的 AAA 结构域意外的不对称排列，并且对其功能至关重要。重建表明 katanin 在开放螺旋和闭合环构象之间循环，这取决于紧张或放松 interprotomer 界面的门控原体的 ATP 占据。这些构象之间的六聚体循环将为微管切断提供动力冲程。