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Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane
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 comp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742854/ https://www.ncbi.nlm.nih.gov/pubmed/29285400 http://dx.doi.org/10.1038/celldisc.2017.49 |
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author | Mu, Zongkai Wang, Lei Deng, Wei Wang, Jiawei Wu, Geng |
author_facet | Mu, Zongkai Wang, Lei Deng, Wei Wang, Jiawei Wu, Geng |
author_sort | Mu, Zongkai |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5742854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57428542017-12-28 Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane Mu, Zongkai Wang, Lei Deng, Wei Wang, Jiawei Wu, Geng Cell Discov Article 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. Nature Publishing Group 2017-12-26 /pmc/articles/PMC5742854/ /pubmed/29285400 http://dx.doi.org/10.1038/celldisc.2017.49 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Mu, Zongkai Wang, Lei Deng, Wei Wang, Jiawei Wu, Geng Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane |
title | Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal
membrane |
title_full | Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal
membrane |
title_fullStr | Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal
membrane |
title_full_unstemmed | Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal
membrane |
title_short | Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal
membrane |
title_sort | structural insight into the ragulator complex which anchors mtorc1 to the lysosomal
membrane |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742854/ https://www.ncbi.nlm.nih.gov/pubmed/29285400 http://dx.doi.org/10.1038/celldisc.2017.49 |
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