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Crystal structure of nucleotide-free dynamin

Nature volume 477, pages 556–560 (2011)Cite this article

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Abstract

Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function.

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Figure 1: Structure of nucleotide-free human dynamin 1.
Figure 2: The dynamin 1 dimer.
Figure 3: Stalk interactions with the BSE and PH domain.
Figure 4: Model for dynamin oligomerization and function.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

The atomic coordinates of human dynamin1 have been deposited in the Protein Data Bank with accession number 3SNH.

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Acknowledgements

This project was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 740/C7 and SFB958/A12 to O.D., SFB740/D7 and SFB958/A04 to F.N., SFB740/C8 and SFB 958/A7 to V.H.), by a Career Development Fellowship of The International Human Frontier Science Program Organization and by the EMBO Young Investigator Program to O.D. We would like to thank S. Werner, M. Papst and S. Kraft for technical assistance, the BESSY staff at BL14.1 for help during data collection, G. Schröder for advice in DEN refinement and U. Heinemann for discussions.

Author information

Author notes

  1. York Posor, Song Gao, Martin Held and Yvette Roske: These authors contributed equally to this work.

Authors and Affiliations

  1. Crystallography, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany ,

    Katja Faelber, Song Gao, Yvette Roske, Dennis Schulze & Oliver Daumke

  2. Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany ,

    York Posor, Song Gao & Volker Haucke

  3. Institute for Mathematics, Freie Universität Berlin, Arnimallee 6, 14195 Berlin, Germany ,

    Martin Held & Frank Noé

  4. Institute for Medical Physics and Biophysics, Charité, Ziegelstraße 5-9, 10117 Berlin, Germany ,

    Oliver Daumke

Authors
  1. Katja Faelber
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Contributions

K.F., Y.P., D.S. and Y.R. performed experiments, K.F., Y.P., S.G., M.H., V.H., F.N. and O.D. designed research, M.H. and. F.N. conducted and analysed molecular modelling and molecular dynamics simulations. K.F. and O.D. wrote the manuscript.

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Correspondence to Katja Faelber or Oliver Daumke.

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Faelber, K., Posor, Y., Gao, S. et al. Crystal structure of nucleotide-free dynamin. Nature 477, 556–560 (2011). https://doi.org/10.1038/nature10369

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