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The crystal structure of dynamin

Nature volume 477, pages 561–566 (2011)Cite this article

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Abstract

Dynamin-related proteins (DRPs) are multi-domain GTPases that function via oligomerization and GTP-dependent conformational changes to play central roles in regulating membrane structure across phylogenetic kingdoms. How DRPs harness self-assembly and GTP-dependent conformational changes to remodel membranes is not understood. Here we present the crystal structure of an assembly-deficient mammalian endocytic DRP, dynamin 1, lacking the proline-rich domain, in its nucleotide-free state. The dynamin 1 monomer is an extended structure with the GTPase domain and bundle signalling element positioned on top of a long helical stalk with the pleckstrin homology domain flexibly attached on its opposing end. Dynamin 1 dimer and higher order dimer multimers form via interfaces located in the stalk. Analysis of these interfaces provides insight into DRP family member specificity and regulation and provides a framework for understanding the biogenesis of higher order DRP structures and the mechanism of DRP-mediated membrane scission events.

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Figure 1: The G397D mutation in Dyn1 ΔPRD blocks self-assembly.
Figure 2: The crystal structure of Dyn1 G397D ΔPRD.
Figure 3: Dyn1 G397D ΔPRD stalk interfaces mediate self-assembly.
Figure 4: Oligomerization of dynamin into helical structures.
Figure 5: Model for dynamin GTP cycle conformational changes.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Atomic coordinates and structure factors for Dyn1 G397D DPRD have been deposited with the Protein Data Bank under accession code 3ZVR.

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Acknowledgements

The authors would like to express thanks to I. Stokes-Rees for assistance with the Wide Space Molecular Replacement, J. Holton for advice and assistance with data collection and H. McMahon for the kind gift of the dynamin clone. We would also like to thank J. Al-Bassam, J. Chappie, A. McCoy, S. Harrison, D. Owen, A. Fisher, E. Baldwin, L. Lackner, G. Adamson, N. Varlakhanova and members of the Nunnari lab for extensive discussions. S.J. is a Damon Runyon Cancer Research Foundation Fellow supported by the Howard Hughes Medical Institute (DRG-2004-09). This work was supported by an American Heart Innovator Award and NIH grants (R01GM062942S1 and R01GM097432) to J.N. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under Contract No. DE-AC02-05CH11231.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, University of California, Davis, Davis, California 95616, USA,

    Marijn G. J. Ford & Jodi Nunnari

  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Simon Jenni

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  1. Marijn G. J. Ford
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Contributions

M.G.J.F. purified, biochemically characterized and crystallized the Dyn1 G397D ΔPRD. M.G.J.F. collected X-ray diffraction data and M.G.J.F. and S.J. solved the structure. M.G.J.F. and J.N. designed experiments and M.G.J.F., S.J. and J.N. interpreted data and prepared the manuscript.

Corresponding author

Correspondence to Jodi Nunnari.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-5 with legends, Supplementary Methods, Supplementary Tables 1-3 and Supplementary References. This file was corrected on 07 October 2011 to change the Protein names from rDyn1 to Dyn1 and Dynamin-1 to Dynamin respectively. (PDF 2774 kb)

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Ford, M., Jenni, S. & Nunnari, J. The crystal structure of dynamin. Nature 477, 561–566 (2011). https://doi.org/10.1038/nature10441

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