4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Huirong Yang1,2,3, Jia Wang4, Mengjie Liu1,2,3
1Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
Protein & Cell
|December 3, 2016
Summary
The study reveals the cryo-electron microscopy structure of human mechanistic target of rapamycin complex 1 (mTORC1). This structure clarifies mTORC1 assembly and provides insights into its regulatory mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a crucial regulator of cell growth, proliferation, translation, autophagy, and metabolism.
- It integrates diverse cellular signals including growth factors, energy status, stress, and amino acid availability.
Purpose of the Study:
- To determine the high-resolution cryo-electron microscopy structure of human mTORC1.
- To elucidate the assembly of the mTORC1 complex and understand its regulatory mechanisms.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was employed to determine the structure of human mTORC1.
- Structural analysis was performed to understand the interactions within the complex and with regulatory molecules.
Main Results:
- The cryo-EM structure of human mTORC1 was determined at 4.4 Å resolution.
- The complex forms a hollow rhomboid shape with 2-fold symmetry, comprising a dimer of (mTOR-Raptor-mLST8) heterotrimers.
- Raptor's N-terminal domain is positioned near mTOR's catalytic cavity, suggesting a role in substrate recognition via TOS motifs.
- FKBP12-Rapamycin binding may sterically hinder substrate access to the mTORC1 catalytic site.
Conclusions:
- The determined structure provides a foundational understanding of mTORC1 assembly.
- It offers a framework for investigating the regulatory mechanisms governing the mTORC1 pathway.
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