Architecture of mTOR protein complex solved

3D model of the protein complex mTORC1. Credit: University of Basel, Biozentrum

For a long time it has been known protein TOR – Target of Rapamycin – controls cell growth and is involved in the development of diseases such as cancer and diabetes. Researchers have now examined the structure of mammalian TOR complex 1 (mTORC1) in more detail.

About 25 years ago, Prof. Michael Hall discovered the protein “Target of Rapamycin” (TOR) at the Biozentrum. It is one of the most studied proteins of the protein kinase family, an important family of regulatory proteins that control many cellular processes. TOR, in mammals called mTOR, is very important for cellular signalling and is implicated in various diseases such as cancer, diabetes, and neurodegeneration. Several mTOR inhibitors have already been approved for therapeutic use, in particular in the treatment of cancer and allograft rejection.

By combining crystallographic methods with cryo-electron microscopy, Prof. Timm Maier’s team together with ETH Zurich researchers have now been able to provide unprecedented insight into the architecture of the protein complex mTORC1. In the cell, the protein kinase mTOR is found in 2 structurally and functionally distinct protein complexes: mTORC1 and mTORC2 in mammals.

Both complexes are giant protein structures consisting of mTOR and other accompanying proteins. In these 2 configurations the protein kinase carries out various functions eg control of cell size and growth, and regulation of metabolism and energy balance. Scientists led by Maier have succeeded in isolating mTORC1 in the quality required for high-resolution cryo-electron microscopy. Using X-ray crystallography they have also been able to determine the structure of the protein Raptor, the second major component of mTORC1.

Each protein plays an important role in the regulation of the activity of the entire complex and the intracellular signalling cascade. “But it doesn’t make sense to examine the individual components alone, as the interactions of all the proteins in the complex are critical for its function,” explains Maier. The finely tuned regulation of mTOR activity is very important because even the smallest disturbances can have serious consequences. Thus, dysregulation in the mTOR signalling pathwa ys plays a role in the development of a number of diseases. https://www.unibas.ch/en/News-Events/News/Uni-Research/Architecture-of-mTOR-protein-complex-solved.html