Open Access4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Author(s) -
Hong Yang,
Jia Wang,
Mengjie Liu,
Xizi Chen,
Min Huang,
Dan Tan,
MengQiu Dong,
Catherine C. L. Wong,
Jiawei Wang,
Yanhui Xu,
Hongwei Wang
Publication year - 2016
Publication title -
protein and cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.973
H-Index - 63
eISSN - 1674-8018
pISSN - 1674-800X
DOI - 10.1007/s13238-016-0346-6
Subject(s) - mtorc1 , mechanistic target of rapamycin , pi3k/akt/mtor pathway , microbiology and biotechnology , autophagy , biology , p70 s6 kinase 1 , chemistry , biophysics , signal transduction , biochemistry , apoptosis
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.