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Structural mechanisms of the mTOR pathway.
Karen Y Linde-Garelli1, Kacper B Rogala1
1Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Current Opinion in Structural Biology
|August 12, 2023
Summary
The mechanistic target of rapamycin (mTOR) pathway regulates cell growth and metabolism. Structural studies reveal how mTOR complexes are activated at membranes, offering insights into disease and potential treatments.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- The mechanistic target of rapamycin (mTOR) signaling pathway is crucial for regulating cellular growth, proliferation, and metabolism in mammals.
- mTOR exists in two distinct complexes, mTORC1 and mTORC2, each with unique downstream targets and functions.
- Dysregulation of the mTOR pathway is linked to various diseases, including cancer and metabolic disorders.
Purpose of the Study:
- To elucidate the structural mechanisms underlying mTOR pathway regulation.
- To understand how mTOR complexes are assembled, localized to membranes, and activated.
- To explore the translational potential of targeting the mTOR pathway for therapeutic development.
Main Methods:
- Recent structural studies utilizing techniques such as cryo-electron microscopy and X-ray crystallography.
- Biochemical assays to investigate protein-protein interactions and substrate recruitment.
- Cellular imaging to track mTOR complex localization and dynamics.
Main Results:
- Detailed molecular insights into how signaling inputs regulate mTOR complex assembly and activation.
- Characterization of the mechanisms by which mTOR complexes are recruited to and function at biological membranes.
- Identification of key structural features involved in substrate binding and phosphorylation.
Conclusions:
- A comprehensive understanding of mTOR structural mechanisms is emerging.
- This knowledge is critical for deciphering the role of mTOR in health and disease.
- Structural insights are paving the way for the development of novel mTOR-targeted therapeutics.
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