Spiral Constriction – How Dynamin Mediates Cellular Nutrient Uptake MDC Researchers Determine the Structure of the ‘Wire-Puller’ Dynamin
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.
The mechanochemical enzyme dynamin is the ‘wire-puller’ that mediates the uptake of nutrients into the cell. However, pathogens also utilize this means to enter the interior of the cell. (A) MDC researchers were able to elucidate the molecular structure of dynamin. If the cell membrane containing the cargo molecules invaginates inward – a process called endocytosis – dynamin self-assembles around the neck of the vesicle in a spiral. (B) Driven by the energy of the cell’s GTP, the vesicle neck is constricted and the vesicle is then pinched off from the cell membrane. (Graphic: Dr. Katja Fälber and M.Sc. Bioinf. Martin Held/Copyright: MDC)
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
http://www.mdc-berlin.de/
