Ring closure activates yeast γTuRC for species-specific microtubule nucleation.

Ring closure activates yeast γTuRC for species-specific microtubule nucleation.
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DOI:
10.1038/nsmb.2953
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发表时间:
2015-02
影响因子:
16.8
通讯作者:
Agard, David A.
Agard, David A.
中科院分区:
生物学1区
文献类型:
--
作者:
Kollman, Justin M.;Greenberg, Charles H.;Li, Sam;Moritz, Michelle;Zelter, Alex;Fong, Kimberly K.;Fernandez, Jose-Jesus;Sali, Andrej;Kilmartin, John;Davis, Trisha N.;Agard, David A.

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微管蛋白环复合体(γ-微管蛋白环复合体,γTURC)是细胞内主要的微管核因子。γTURC是由重复的γ-微管蛋白小复合体(γTUSC)亚基组装而成,被认为是通过呈现模仿微管几何形状的γ-微管蛋白环来发挥模板的作用。然而,以前的酵母γTURC结构显示γTUSC处于开放构象中,这阻止了与微管对称性的匹配。相反,我们在这里表明,当γ-微管蛋白复合体附着在微管上时,它处于封闭的构象中。为了确认其功能重要性,我们捕获了关闭状态并确定了其结构,表明γ-微管蛋白环与微管对称性精确匹配,并提供了对γTURC结构的详细了解。重要的是,闭合状态是一个更强的成核剂,这表明这种构象开关可能以变构方式控制γ的TURC活性。最后,我们证明了γTurcs对来自同一物种的微管蛋白有深刻的偏好。
The γ-tubulin ring complex (γTuRC) is the primary microtubule nucleator in cells. γTuRC is assembled from repeating γ-tubulin small complex (γTuSC) subunits and is thought to function as a template by presenting a γ-tubulin ring that mimics microtubule geometry. However, a previous yeast γTuRC structure showed γTuSC in an open conformation that prevents matching to microtubule symmetry. By contrast, we show here that γ-tubulin complexes are in a closed conformation when attached to microtubules. To confirm its functional importance we trapped the closed state and determined its structure, showing that the γ-tubulin ring precisely matches microtubule symmetry and providing detailed insight into γTuRC architecture. Importantly, the closed state is a stronger nucleator, suggesting this conformational switch may allosterically control γTuRC activity. Finally, we demonstrate that γTuRCs have a profound preference for tubulin from the same species.
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