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4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structur...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Higher Education Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5205667/ https://www.ncbi.nlm.nih.gov/pubmed/27909983 http://dx.doi.org/10.1007/s13238-016-0346-6 |
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author | Yang, Huirong Wang, Jia Liu, Mengjie Chen, Xizi Huang, Min Tan, Dan Dong, Meng-Qiu Wong, Catherine C. L. Wang, Jiawei Xu, Yanhui Wang, Hong-Wei |
author_facet | Yang, Huirong Wang, Jia Liu, Mengjie Chen, Xizi Huang, Min Tan, Dan Dong, Meng-Qiu Wong, Catherine C. L. Wang, Jiawei Xu, Yanhui Wang, Hong-Wei |
author_sort | Yang, Huirong |
collection | PubMed |
description | Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase-like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for substrate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance for substrate entry to the catalytic cavity of mTORC1. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regulatory mechanism of mTORC1 pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0346-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5205667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Higher Education Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52056672017-01-18 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 Yang, Huirong Wang, Jia Liu, Mengjie Chen, Xizi Huang, Min Tan, Dan Dong, Meng-Qiu Wong, Catherine C. L. Wang, Jiawei Xu, Yanhui Wang, Hong-Wei Protein Cell Research Article Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase-like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for substrate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance for substrate entry to the catalytic cavity of mTORC1. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regulatory mechanism of mTORC1 pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0346-6) contains supplementary material, which is available to authorized users. Higher Education Press 2016-12-01 2016-12 /pmc/articles/PMC5205667/ /pubmed/27909983 http://dx.doi.org/10.1007/s13238-016-0346-6 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Article Yang, Huirong Wang, Jia Liu, Mengjie Chen, Xizi Huang, Min Tan, Dan Dong, Meng-Qiu Wong, Catherine C. L. Wang, Jiawei Xu, Yanhui Wang, Hong-Wei 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title | 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title_full | 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title_fullStr | 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title_full_unstemmed | 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title_short | 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1 |
title_sort | 4.4 å resolution cryo-em structure of human mtor complex 1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5205667/ https://www.ncbi.nlm.nih.gov/pubmed/27909983 http://dx.doi.org/10.1007/s13238-016-0346-6 |
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