Crystal Structure of the Gtr1pGTP-Gtr2pGDP Protein Complex Reveals Large Structural Rearrangements Triggered by GTP-to-GDP Conversion
Crystal Structure of the Gtr1pGTP-Gtr2pGDP Protein Complex Reveals Large Structural Rearrangements Triggered by GTP-to-GDP Conversion
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DOI：
10.1074/jbc.c112.384420
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发表时间：
2012-08-24
影响因子：
4.8
通讯作者：
Kim, Yeon-Gil
中科院分区：
文献类型：
--
作者：
Jeong, Jae-Hee;Lee, Kwang-Hoon;Kim, Yeon-Gil
由 RagA（或 RagB）和 RagC（或 RagD）组成的异二聚体 Rag GTPases 是响应氨基酸水平激活雷帕霉素复合物 1 (TORC1) 靶标的关键调节因子。负载 GTP 的 RagA/B 和负载 GDP 的 RagC/D 之间的异二聚体是结合 Raptor 并导致 TORC1 激活的最活跃形式。在这里，我们展示了活性酵母 Rag GTPase 异二聚体 Gtr1pGTP-Gtr2pGDP 的晶体结构。该结构表明，Gtr2p 上的 GTP 到 GDP 的转换导致该亚基发生大的构象转变，包括长片段的大规模重排，该长片段在 RagA 中的相应区域参与与 Raptor 的结合。此外，异源二聚体的两个 GTPase 结构域相互接触，但不会引起 Gtr1p 亚基的任何构象变化。这些特征解释了两个 GTPases 亚基的核苷酸结合状态如何打开和关闭 Raptor 结合亲和力。
The heterodimeric Rag GTPases consisting of RagA (or RagB) and RagC (or RagD) are the key regulator activating the target of rapamycin complex 1 (TORC1) in response to the level of amino acids. The heterodimer between GTP-loaded RagA/B and GDP-loaded RagC/D is the most active form that binds Raptor and leads to the activation of TORC1. Here, we present the crystal structure of Gtr1pGTP-Gtr2pGDP, the active yeast Rag GTPase heterodimer. The structure reveals that GTP-to-GDP conversion on Gtr2p results in a large conformational transition of this subunit, including a large scale rearrangement of a long segment whose corresponding region in RagA is involved in binding to Raptor. In addition, the two GTPase domains of the heterodimer are brought to contact with each other, but without causing any conformational change of the Gtr1p subunit. These features explain how the nucleotide-bound statuses of the two GTPases subunits switch the Raptor binding affinity on and off.