Spiral constriction -- how dynamin mediates cellular nutrient uptake

Sep 20, 2011

Dr. Katja Falber and Professor Oliver Daumke, structural biologists at the Max Delbruck 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.

Many nutrients pass from the blood through cell membrane channels into the body . 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 , 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.

Explore further: Environmental pollutants make worms susceptible to cold

More information: Nature, DOI: 10.1038/nature10369

add to favorites email to friend print save as pdf

Related Stories

Crystal structure shows how motor protein works

Sep 18, 2011

The crystal structure of the dynamin protein — one of the molecular machines that makes cells work — has been revealed, bringing insights into a class of molecules with a wide influence on health and disease.

The downside of microtubule stability

Jun 15, 2009

Stalled microtubules might be responsible for some cases of the neurological disorder Charcot-Marie-Tooth (CMT) disease, Tanabe and Takei report in the Journal of Cell Biology . A mutant protein makes the mi ...

Researchers clock the speed of brain signals

Jun 22, 2011

Two studies featuring research from Weill Cornell Medical College have uncovered surprising details about the complex process that leads to the flow of neurotransmitters between brain neurons -- a dance of ...

Recommended for you

Environmental pollutants make worms susceptible to cold

Sep 19, 2014

Some pollutants are more harmful in a cold climate than in a hot, because they affect the temperature sensitivity of certain organisms. Now researchers from Danish universities have demonstrated how this ...

Interactions of Earth's smallest players have global impact

Sep 19, 2014

A new study reveals the interactions among bacteria and viruses that prey on them thriving in oxygen minimum zones—stretches of ocean starved for oxygen that occur around the globe. Understanding such microbial ...

A new quality control pathway in the cell

Sep 18, 2014

Proteins are important building blocks in our cells and each cell contains millions of different protein molecules. They are involved in everything from structural to regulatory aspects in the cell. Proteins are constructed ...

User comments : 0