Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex.
Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex.
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DOI：
10.1016/j.molcel.2017.10.016
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发表时间：
2017-12-07
期刊：
影响因子：
16
通讯作者：
Hurley JH
中科院分区：
文献类型：
--
作者：
Su MY;Morris KL;Kim DJ;Fu Y;Lawrence R;Stjepanovic G;Zoncu R;Hurley JH
溶酶体膜是感知细胞营养水平的位点，其通过Rag GTP酶和Ragulator复合物转导为mTORC 1。在1.4 nm分辨率下测定了五亚基人Ragulator的晶体结构。Lamtor 1包裹在其他四个子单元周围以稳定组装。Lamtor 2：Lamtor 3二聚体堆叠在Lamtor 4：Lamtor 5上以产生Rag结合的平台。氢-氘交换被用来映射的Rag结合位点的外表面的Lamtor 2：Lamtor 3二聚体和N-末端固有的无序区域的Lamtor 1。使用EM以16 μ m分辨率重建与Ragulator结合的全长RagAGTP：RagCGDP二聚体的组装，揭示Rags的G结构域远离Ragulator核心突出。组合的结构模型显示了Ragulator如何作为一个平台来呈现用于mTORC 1募集的活性Rags，并且可能表明Rag GEF活性的非常规机制。
The lysosomal membrane is the locus for sensing cellular nutrient levels, which are transduced to mTORC1 via the Rag GTPases and the Ragulator complex. The crystal structure of the five-subunit human Ragulator at 1.4 Å resolution was determined. Lamtor1 wraps around the other four subunits to stabilize the assembly. The Lamtor2:Lamtor3 dimer stacks upon Lamtor4:Lamtor5 to create a platform for Rag binding. Hydrogen-deuterium exchange was used to map the Rag binding site to the outer face of the Lamtor2:Lamtor3 dimer and to the N-terminal intrinsically disordered region of Lamtor1. EM was used to reconstruct the assembly of the full-length RagAGTP:RagCGDP dimer bound to Ragulator at 16 Å resolution, revealing that the G-domains of the Rags project away from the Ragulator core. The combined structural model shows how Ragulator functions as a platform for the presentation of active Rags for mTORC1 recruitment, and might suggest an unconventional mechanism for Rag GEF activity.
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影响因子：
48
作者：
Barad BA;Echols N;Wang RY;Cheng Y;DiMaio F;Adams PD;Fraser JS
通讯作者：
Fraser JS
DOI：
10.1126/science.aag1417
发表时间：
2017-03-24
期刊：
Science (New York, N.Y.)
影响因子：
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发表时间：
2006-11-01
影响因子：
3.2
作者：
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影响因子：
64.8
作者：
Kawashima, T;BerthetColominas, C;Leberman, R
通讯作者：
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影响因子：
7.4
作者：
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