MDC and MHH Researchers Show How Dynamin Mediates Membrane Constriction and Scission – A Vital Process
2015-08-25 / Cells continually form membrane vesicles that are released into the cell. If this vital process is disturbed, nerve cells, for example, cannot communicate with each other. The protein molecule dynamin is essential for the regulated formation and release of many vesicles. Scientists of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and the Institute for Biophysical Chemistry of Hannover Medical School (MHH), together with researchers from the Freie Universität Berlin and the Leibniz-Institut für Molekulare Pharmakologie (FMP), have now elucidated the regulated process by which the molecular “motor” dynamin assembles into a screw-like structure. Moreover, they demonstrated how specific mutations impair the function of dynamin, for example in the congenital muscle disorder centronuclear myopathy or the neuropathy Charcot-Marie-Tooth disease (Nature, doi:10.1038/nature14880)**. The researchers’ study represents an important contribution to the development of new therapeutic approaches.
Professor Oliver Daumke and Dr. Katja Fälber (Photo: private)
To transmit signals, nerve cells release neurotransmitters that are packed in vesicles. These vesicles are formed through membrane invaginations of the cell wall which are constricted and severed by dynamin. First, a chain of dynamin molecules wraps around the neck of the budding vesicle in a spiral. In a second energy-dependent step, the dynamin spiral is constricted, and the vesicle is released into the cell.
The researchers elucidated the 3-dimensional structure of the basic component of the spiral. It consists of four dynamin molecules, called a dynamin tetramer. "For the first time we could determine how the dynamin tetramers assemble into a spiral," said Dr. Katja Fälber from the Crystallography Department of the MDC. "The structure also explains why this process only occurs on membranes: Only there do rearrangements in the dynamin tetramer take place that release the contacts for spiral formation," said Professor Oliver Daumke.
**Crystal structure of the dynamin tetramer
Thomas F. Reubold1*, Katja Faelber2*, Nuria Plattner3§, York Posor4§, Katharina Branz4, Ute Curth1,5, Jeanette Schlegel2, Roopsee Anand1, Dietmar J. Manstein1,5, Frank Noé3, Volker Haucke4,6, Oliver Daumke2,6 & Susanne Eschenburg1
1Medizinische Hochschule Hannover, Institut für Biophysikalische Chemie, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2Max-Delbrück-Centrum für Molekulare Medizin, Kristallographie, Robert-Rössle-Straße 10, 13125 Berlin, Germany
3Freie Universität Berlin, Institut für Mathematik, Arnimallee 6, 14195 Berlin, Germany
4Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Straße 10, 13125 Berlin, Germany
5Medizinische Hochschule Hannover, Forschungseinrichtung Strukturanalyse, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
6Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 6, 14195 Berlin, Germany
* These authors contributed equally to this work.