Architecture of cellular control center mTORC2 elucidated

February 20, 2018

The protein complex mTORC2 controls cellular lipid and carbohydrate metabolism. Researchers from the Biozentrum of the University of Basel and the ETH Zurich have now succeeded in deciphering the 3D structure of this important protein complex. The results have recently been published in eLife.

The protein complex mTORC2 plays a crucial role in the regulation of cellular metabolism. It stimulates, for example, the production of lipids and fatty acids, but it also controls carbohydrate metabolism. In the past, studies have shown that mTORC2 promotes tumor growth due to increased lipid production and that it is involved in the development of diabetes.

The term mTORC2 derives from the fact that two such complexes exist in the cell. The two complexes, mTORC1 and mTORC2, are composed of different proteins, with the protein mTOR - "Target of Rapamycin" - as the central component.

Structure of mTORC2 solved

Using Nobel prize-winning cryo-electron microscopy, the scientists led by Prof. Timm Maier and Prof. Michael Hall from the Biozentrum of the University of Basel as well as Prof. Nenad Ban, ETH Zurich, have been able to visualize the three-dimensional structure of the mTORC2 protein complex in its assembled state.

"For the first time, we have obtained a 3D image of mTORC2 at intermediate resolution," says Maier. "This picture not only reveals the basic shape of the complex, but also the interaction sites of accessory proteins with mTOR." The two complexes, mTORC1 and mTORC2, are distinguished by accessory partner proteins of mTOR. This explains why the protein mTOR in its two complexes can perform distinct tasks in the cell.

The mTORC2 protein complex is one of the largest structures in the cell. It is about twenty times larger than a typical protein. But despite its size, it is still quite flexible and dynamic. "Its individual components move in different directions," describes Maier. "Therefore, it was quite challenging to obtain a good quality 3D image of its structure."

3D structure as basis for drug development

The 3D structure of a protein determines its function. Based on this structure, the researchers have made an important step towards investigating how mTORC2 recognizes its substrates and changes its shape as well as how the protein complex transmits signals in the cell.

"mTORC1 and mTORC2 signaling is linked to many diseases, but up to now there are no specific mTORC2 inhibitors available," says Maier. "The structural insights may facilitate the search for such drugs."

University of Basel

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to