Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Architecture of mTOR Protein Complex Solved

18.12.2015

For a long time it has been known that the protein TOR – Target of Rapamycin – controls cell growth and is involved in the development of diseases such as cancer and diabetes. Researchers at the University of Basel’s Biozentrum together with scientists from ETH Zurich have now examined the structure of mammalian TOR complex 1 (mTORC1) in more detail. The scientists have revealed its unique architecture in their latest publication in “Science”.

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.


3D model of the protein complex mTORC1.

University of Basel, Biozentrum

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.

However, despite extensive research on TOR over the last decades, attempts to uncover the detailed structure of the protein kinase and its partners have been unsuccessful. By combining crystallographic methods with cryo-electron microscopy, Prof. Timm Maier’s team together with researchers of the ETH Zurich have now been able to provide unprecedented insight into the architecture of the protein complex mTORC1.

Structure of mTORC1 elucidated

In the cell, the protein kinase mTOR is found in two structurally and functionally distinct protein complexes termed mTORC1 and mTORC2 in mammals. Both complexes are giant protein structures consisting of mTOR and other accompanying proteins. In these two configurations the protein kinase carries out various functions such as the control of cell size and growth, as well as the regulation of metabolism and energy balance.

mTOR itself is one of the largest proteins in the cell and when combined with other proteins even larger. This makes it quite difficult to investigate its structure. “The partner proteins of mTOR have already been identified in earlier biochemical studies”, says Maier.

“However, it has remained unclear how the proteins interact precisely.” After more than three years of work, the 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.

Accompanying proteins important for function

"Although there is much known about mTORC1, our study revealed surprising new insight”, states Maier. "The architecture of this huge protein complex is quite exceptional. We could determine the precise interaction sites of the partner proteins and how they are arranged, and thus elucidate the function of the individual partners.” In fact, each protein plays an important role in the regulation of the activity of the entire complex and the intracellular signalling cascade.

More than the sum of its parts

With their study, the researchers have provided the basis for further investigations. Now the researchers will be able to investigate the function of each individual protein in the complex in more detail. “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 whole is much more than the sum of its parts.” 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 pathways plays a role in the development of a number of diseases.

Original source

Christopher H.S. Aylett, Evelyn Sauer, Stefan Imseng, Daniel Boehringer, Michael N. Hall, Nenad Ban and Timm Maier
Architecture of Human mTOR Complex 1
Science, published online 17 December 2015.

Further information

Prof. Dr. Timm Maier, University of Basel, Biozentrum, tel. +41 61 267 21 76, email: timm.maier@unibas.ch

Dr. Katrin Bühler, University of Basel, Biozentrum, Communications, tel. +41 61 267 09 74, email: katrin.buehler@unibas.ch

Weitere Informationen:

https://www.unibas.ch/en/News-Events/News/Research/Architecture-of-mTOR-Protein-...

Katrin Bühler | Universität Basel

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>