Cryo-EM of the dynamin polymer assembled on lipid membrane

Leopold Kong, Kem A. Sochacki, Huaibin Wang, Shunming Fang, Bertram Canagarajah, Andrew D. Kehr, William J. Rice, Marie-Paule Strub, Justin W. Taraska and Jenny E. Hinshaw ()
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Leopold Kong: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Kem A. Sochacki: National Heart, Lung, and Blood Institute, NIH
Huaibin Wang: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Shunming Fang: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Bertram Canagarajah: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Andrew D. Kehr: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
William J. Rice: New York Structural Biology Center
Marie-Paule Strub: National Heart, Lung, and Blood Institute, NIH
Justin W. Taraska: National Heart, Lung, and Blood Institute, NIH
Jenny E. Hinshaw: National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Nature, 2018, vol. 560, issue 7717, 258-262

Abstract: Abstract Membrane fission is a fundamental process in the regulation and remodelling of cell membranes. Dynamin, a large GTPase, mediates membrane fission by assembling around, constricting and cleaving the necks of budding vesicles1. Here we report a 3.75 Å resolution cryo-electron microscopy structure of the membrane-associated helical polymer of human dynamin-1 in the GMPPCP-bound state. The structure defines the helical symmetry of the dynamin polymer and the positions of its oligomeric interfaces, which were validated by cell-based endocytosis assays. Compared to the lipid-free tetramer form2, membrane-associated dynamin binds to the lipid bilayer with its pleckstrin homology domain (PHD) and self-assembles across the helical rungs via its guanine nucleotide-binding (GTPase) domain3. Notably, interaction with the membrane and helical assembly are accommodated by a severely bent bundle signalling element (BSE), which connects the GTPase domain to the rest of the protein. The BSE conformation is asymmetric across the inter-rung GTPase interface, and is unique compared to all known nucleotide-bound states of dynamin. The structure suggests that the BSE bends as a result of forces generated from the GTPase dimer interaction that are transferred across the stalk to the PHD and lipid membrane. Mutations that disrupted the BSE kink impaired endocytosis. We also report a 10.1 Å resolution cryo-electron microscopy map of a super-constricted dynamin polymer showing localized conformational changes at the BSE and GTPase domains, induced by GTP hydrolysis, that drive membrane constriction. Together, our results provide a structural basis for the mechanism of action of dynamin on the lipid membrane.

Keywords: Dynamin Polymer; GTPase Domain; Helical Polymers; Membrane Constriction; Helical Symmetry (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0378-6

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