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-Structure paper
| タイトル | Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex. |
|---|---|
| ジャーナル・号・ページ | Mol Cell, Vol. 68, Issue 5, Page 835-846.e3, Year 2017 |
| 掲載日 | 2017年12月7日 |
著者 | Ming-Yuan Su / Kyle L Morris / Do Jin Kim / Yangxue Fu / Rosalie Lawrence / Goran Stjepanovic / Roberto Zoncu / James H Hurley / ![]() |
| PubMed 要旨 | 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 ...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 RagA:RagC 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. |
リンク | Mol Cell / PubMed:29107538 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 1.42 - 16.2 Å |
| 構造データ | ![]() EMDB-7072: ![]() PDB-6b9x: |
| 化合物 | ![]() ChemComp-HOH: |
| 由来 |
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キーワード | SIGNALING PROTEIN / Ragulator / Lamtor |
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