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Three-dimensional reconstruction of dynamin in the constricted state

Nature Cell Biology volume 3, pages 922–926 (2001)Cite this article

Abstract

Members of the dynamin family of GTPases have unique structural properties that might reveal a general mechanochemical basis for membrane constriction. Receptor-mediated endocytosis, caveolae internalization and certain trafficking events in the Golgi all require dynamin for vesiculation1. The dynamin-related protein Drp1 (Dlp1) has been implicated in mitochondria fission2 and a plant dynamin-like protein phragmoplastin is involved in the vesicular events leading to cell wall formation3. A common theme among these proteins is their ability to self-assemble into spirals and their localization to areas of membrane fission. Here we present the first three-dimensional structure of dynamin at a resolution of ∼20 Å, determined from cryo-electron micrographs of tubular crystals in the constricted state. The map reveals a T-shaped dimer consisting of three prominent densities: leg, stalk and head. The structure suggests that the dense stalk and head regions rearrange when GTP is added, a rearrangement that generates a force on the underlying lipid bilayer and thereby leads to membrane constriction. These results indicate that dynamin is a force-generating 'contrictase'.

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Figure 1: Electron micrographs of negatively stained ΔPRD dynamin tubes and spirals.
Figure 2: Three-dimensional reconstruction of constricted ΔPRD dynamin tubes.
Figure 3: Domain arrangement of ΔPRD dynamin dimer.
Figure 4: Docking the crystal structures of the PH domain of dynamin17 and the GTPase domain of hGBP1 (ref. 19).

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Acknowledgements

We thank J. Hanover for helpful suggestions and critical reading of the manuscript; workers in S. Schmid's laboratory for providing ΔPRD high titre stock; R. Milligan and A. Lin for assistance with Phoelix and VolVis; B. Sheehan for general computer help; N. Unwin for the use of the MRC helix-processing package; B. Carragher and D. Weber for help with Suprim; A. Steven and M. Cerritelli for assistance with the STEM analysis; B. Bowers for the rotary shadowing work; and F. Dyda, D. Belnap and T. Hirai for help with O. The BNL STEM is an NIH Supported Resource Center, with additional support provided by the Department of Energy, Office of Biological and Environmental Research.

Author information

Authors and Affiliations

  1. Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Building 8, Room 419, MSC 0851, 8 Center Drive

    Peijun Zhang & Jenny E. Hinshaw

  2. National Institutes of Health, Bethesda, 20892, Maryland, USA

    Peijun Zhang & Jenny E. Hinshaw

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  1. Peijun Zhang
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  2. Jenny E. Hinshaw
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Correspondence to Jenny E. Hinshaw.

Supplementary information

Supplementary movie

Movie 1 Quarter map of ΔPRD dynamin three-dimensional structure. The map shows two legs, one in front of the other, connected to the stalk region by a narrow linker. The stalk consists of a very dense globular domain that extends and bifurcates into two heads. The head has a distinct contour shape that accommodates the GTPase crystal structure (see Movie 2). (MOV 631 kb)

Supplementary movie

Movie 2 Docking the two crystal structures (PH17 and GTPase19) into the ΔDDPRD dynamin three-dimensional map.The movie demonstrates that GTPase (green) and PH (orange) crystal structures fit very well into the head and leg domains respectively. (MOV 565 kb)

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Zhang, P., Hinshaw, J. Three-dimensional reconstruction of dynamin in the constricted state. Nat Cell Biol 3, 922–926 (2001). https://doi.org/10.1038/ncb1001-922

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