Dr. Katja Flber and Professor Oliver Daumke, structural biologists at the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch, together with researchers from Freie Universitt (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. Flber, together with the endocytosis researcher Professor Volker Haucke and the bioinformatician Dr. Frank No 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 dyn
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