Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Inner Life of a Giant - Max Planck Researchers Gain New Insights into Protein Degradation

04.04.2012
Uncontrolled or inaccurate degradation of cellular proteins can lead to diseases like cancer or Alzheimer’s disease.

Scientists of the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, have now uncovered the structure and the operating mechanism of an important component of the human cellular degradation machinery, tripeptidyl peptidase II (TPPII).


3D-model of the active human TPPII-complex
Graphic: Beate Rockel/Copyright: MPI of Biochemistry

“Decoding the structure of TPPII is a crucial milestone towards understanding the complex activation and control of protein degradation”, says Beate Rockel, scientist at the MPIB. The results of the study have now been published in the journal Structure.

Proteins, the molecular building blocks and machines of the cell, are composed of long chains of amino acids. When such a chain has to be degraded, it is first unfolded and then cleaved into shorter pieces, so-called peptides. Tripeptidyl peptidase II (TPPII), which was analyzed by scientists in the department of MPIB director Wolfgang Baumeister, is one of the factors that take over further degradation. It chops the peptides into even smaller bits which, after some additional steps, can be recycled for the assembly of new proteins. TPPII is a large complex consisting of 32 to 40 identical subunits, which are inactive on their own. The complex becomes functional, when the subunits join into two strands twisted around each other. The complex is approximately 100 times larger than most other protein-degrading enzymes. “TPPII is a real giant amongst cellular proteins”, says PhD student Anne-Marie Schönegge. “Solving the structure of such a colossus is a difficult task.”

Bit by Bit towards the Complete Structure
The researchers of the MPIB combined different methods of structural biology and models to determine the structure and operating mechanism of TPPII in detail. In collaboration with scientists from the Lawrence Berkeley National Laboratory in Berkeley, they had successfully solved the atomic structure of TPPII-subunits of the fruit fly by X-ray-crystallography. In a subsequent step, this structure served as the basis to calculate a model of human TPPII-subunits.

Using cryoelectron microscopy and single-particle reconstruction, the scientists were able to determine the structure of complete and active TPPII-complexes of the fruit fly and humans – but only at medium resolution. By combining the structure of the complete complexes with the more detailed atomic models of individual subunits, the co-workers of the research department “Molecular Structural Biology” could now solve the detailed structural organization of human TPPII: the subunits enclose a cavity system which traverses the whole TPPII complex and harbors the catalytic sites.
By fitting the structures of the inactive subunits into the structure of the active complex, the scientists pinpointed regions that are supposed to undergo changes upon activation of TPPII. These regions include the active site and the entrances into the cavity-system inside the complex. Beate Rockel also hopes for other benefits out of this work: “Insights into the TPPII structure could contribute to the development of new drugs in the future, since there are indications that TPPII may be involved in diseases such as muscle wasting, adiposis and cancer.” [VS]

Original publications
Schönegge, A., Villa, E., Hegerl, R., Peters, J., Förster, F., Baumeister, W. and Rockel, B.: The structure of human tripeptidyl peptidase II as determined by a hybrid approach. Structure 20(4): 593–603, April 4, 2012
DOI: 10.1016/j.str.2012.01.025

Chuang, C. K., Rockel, B., Seyit, G., Walian, P. J., Schönegge, A., Peters, J., Zwart, P. H., Baumeister, W. and Jap, B. K.: Hybrid molecular structure of the giant protease tripeptidyl peptidase II. Nat Struct Mol Biol 17(8): 990-996, August 1, 2010
DOI: 10.1038/nsmb.1870

Contact
Prof. Dr. Wolfgang Baumeister
Molecular Structural Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
E-Mail: baumeist@biochem.mpg.de
http://www.biochem.mpg.de/baumeister

Dr. Beate Rockel
Molecular Structural Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
E-Mail: rockel@biochem.mpg.de

Anja Konschak
Public Relations
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Phone: +49 (0) 89 8578-2824
E-Mail: konschak@biochem.mpg.de
http://www.biochem.mpg.de

Anja Konschak | Max-Planck-Institut
Further information:
http://www.biochem.mpg.de/en/news/pressroom/index.html
http://www.biochem.mpg.de/baumeister/

More articles from Life Sciences:

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

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,...

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

Will Earth still exist 5 billion years from now?

08.12.2016 | Physics and Astronomy

Oxygen can wake up dormant bacteria for antibiotic attacks

08.12.2016 | Health and Medicine

Newly discovered bacteria-binding protein in the intestine

08.12.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>