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首页> 外文期刊>Cell discovery. >Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane
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Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane

机译：对Ragulator复合物的结构见解，该复合物将mTORC1锚定在溶酶体膜上

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The mechanistic target of rapamycin (mTOR) signal-transduction pathway plays a key role in regulating many aspects of metabolic processes. The central player of the mTOR signaling pathway, mTOR complex 1 (mTORC1), is recruited by the pentameric Ragulator complex and the heterodimeric Rag GTPase complex to the lysosomal membrane and thereafter activated. Here, we determined the crystal structure of the human Ragulator complex, which shows that Lamtor1 possesses a belt-like shape and wraps the other four subunits around. Extensive hydrophobic interactions occur between Lamtor1 and the Lamtor2-Lamtor3, Lamtor4-Lamtor5 roadblock domain protein pairs, while there is no substantial contact between Lamtor2-Lamtor3 and Lamtor4-Lamtor5 subcomplexes. Interestingly, an α-helix from Lamtor1 occupies each of the positions on Lamtor4 and Lamtor5 equivalent to the α3-helices of Lamtor2 and Lamtor3, thus stabilizing Lamtor4 and Lamtor5. Structural comparison between Ragulator and the yeast Ego1-Ego2-Ego3 ternary complex (Ego-TC) reveals that Ego-TC only corresponds to half of the Ragulator complex. Coupling with the fact that in the Ego-TC structure, Ego2 and Ego3 are lone roadblock domain proteins without another roadblock domain protein pairing with them, we suggest that additional components of the yeast Ego complex might exist.
机译：雷帕霉素（mTOR）信号转导途径的机械目标在调节代谢过程的许多方面起着关键作用。 mTOR信号通路的核心参与者mTOR复合物1（mTORC1）被五聚体Ragulator复合物和异二聚体Rag GTPase复合物募集到溶酶体膜中，然后被激活。在这里，我们确定了人类Ragulator复合物的晶体结构，这表明Lamtor1具有带状形状，并将其他四个亚单位包裹起来。 Lamtor1和Lamtor2-Lamtor3，Lamtor4-Lamtor5障碍域蛋白对之间发生广泛的疏水相互作用，而Lamtor2-Lamtor3和Lamtor4-Lamtor5亚复合物之间没有实质性的接触。有趣的是，来自Lamtor1的一个α螺旋占据了Lamtor4和Lamtor5上每个相当于Lamtor2和Lamtor3的α3螺旋的位置，从而稳定了Lamtor4和Lamtor5。 Ragulator与酵母Ego1-Ego2-Ego3三元复合物（Ego-TC）之间的结构比较显示，Ego-TC仅对应于Ragulator复合物的一半。结合以下事实：在Ego-TC结构中，Ego2和Ego3是单独的路障域蛋白，而没有与之配对的其他路障域蛋白，我们建议可能存在酵母Ego复合体的其他成分。

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