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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>