Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Spiral Constriction – How Dynamin Mediates Cellular Nutrient Uptake MDC Researchers Determine S

20.09.2011
Dr. Katja Fälber and Professor Oliver Daumke, structural biologists at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, together with researchers from Freie Universität (FU) Berlin, have determined the molecular structure of dynamin, a ‘wire-puller’ that mediates nutrient uptake into the cell.
Since pathogens such as HIV can also enter the body’s cells in this way, understanding the underlying molecular mechanisms can potentially open up new approaches for medical applications (Nature, DOI: 10.1038/nature10369)*.

Many nutrients pass from the blood through cell membrane channels into the body cells. However, appropriate channels do not exist for all nutrients.

For example, iron binds outside the cell to a large transport molecule and is imported by other means, via endocytosis, into the cell. The cargo-containing transport molecules bind to the cell membrane, which invaginates inward. The iron molecules along with their transporters are taken up in a small membrane bubble (vesicle) into the cell and released there.

An important ‘wire-puller’ of endocytosis is the protein molecule dynamin. And that in the most literal sense of the word: If a vesicle forms, the dynamin molecules self-assemble and form a spiral around the neck of the vesicle. Dynamin functions like a small motor: It uses the energy of the cell’s GTP to pull the spiral together, constricting the neck of the vesicle so that it detaches from the cell membrane.

The molecular details of this ‘pull’ mechanism around the vesicle neck were previously unknown. In their present study, MDC structural biologists Professor Daumke and Dr. Fälber, together with the endocytosis researcher Professor Volker Haucke and the bioinformatician Dr. Frank Noé of FU Berlin, provide fundamental insights into this process. Using X-ray diffraction analysis, they succeeded in building a structural model of dynamin. For this study it was necessary to produce protein crystals of dynamin. To achieve this, the researchers utilized the insights gained in their previous study about a dynamin-related protein. From the X-ray diffraction pattern of these crystals the researchers were then able to derive a detailed picture of dynamin. “Now that we have an idea of how the dynamin molecule is structured, we can understand at the atomic level how the molecular motor dynamin functions,” said Professor Daumke.

In addition to nutrient uptake, endocytosis is also essential for the transmission of signals between neighboring nerve cells and for the immune system. In this way, for example, macrophages engulf pathogens and make them harmless. Professor Daumke: “However, pathogens like HIV and influenza viruses utilize endocytosis to enter our body cells and to spread there. That is why it is important to gain an even more detailed understanding of the molecular ‘pull’ mechanism of dynamin during endocytosis. Then we can find potential approaches for medical applications – especially for patients with muscle and nerve disorders associated with mutations in the dynamin gene.” In future research projects funded by the German Research Foundation within the framework of the Collaborative Research Centers (SFB740 and SFB958), the MDC researchers intend to take an even closer look at dynamin. They want to find out what structural changes dynamin accomplishes when the cell’s energy carrier GTP binds to the protein and the ‘pull’ mechanism is set in motion at the vesicle neck.

*Crystal structure of nucleotide-free dynamin
Katja Faelber1, York Posor2#, Song Gao1,2#, Martin Held3#, Yvette Roske1#, Dennis Schulze1, Volker Haucke2, Frank Noé3 & Oliver Daumke1,4
1Crystallography, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
2Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
3Institute for Mathematics, Freie Universität Berlin, Arnimallee 6, 14195 Berlin, Germany.
4Institute for Medical Physics and Biophysics, Charité, Ziegelstraße 5-9, 10117 Berlin, Germany.

#These authors contributed equally to this work.

Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10
13125 Berlin
Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>