Membrane constriction by Dynamin

The Dynamin tetramer binds a membrane and forms a filament, a right-handed helix around a membrane tube. The proposed stepping mechanism for membrane constriction involves a power stroke, that pulls the helical turns against each other, each step reducing the membrane tube radius by approximately 1 nm.
The animation introduces the domain structure of dynamin and the way it forms dimers and then a tetramer out of two dimers. The helical filament formation is shown from the front and the top, followed by the dimer formation of two G-domains from neighbouring turns. For the first power stroke the sequence of events are shown individually, for the second and third steps in a more synchronous coincidential way.

This was a project for and with Katja Faelber, Jeffrey Noel and Oliver Daumke - Max Delbrück Center for Molecular Medicine (MDC), Berlin.

status: 2019

Dynamin is a five-domain protein, four of which have been structurally characterized. GTP binding shifts the G-domain/BSE to an open conformation. The Stalk domains mediate the formation of a stable dimer. The dimer mediates further oligomerization through its tetramer interface. In solution, oligomerization stops with the tetramer. The PH-domains mediate membrane binding. Localization to the membrane opens up the tetrameric interface for filament formation. The tetramer has a naturally curved shape, corresponding to the curvature of tight membrane necks, but can additionally adjust its curvature. The filament forms a right-handed helix around a membrane tube. The proposed stepping mechanism for membrane constriction: After one helical turn has formed, GTP-bound G-domains from neighbouring turns dimerize. Dimerization activates GTP hydrolysis, which generates a strong shift in the G-domain/ BSE to the closed conformation. This re-arrangement comprises the power stroke, pulling the helical turns against each other. This constricts the underlying membrane tube. After phosphate release the GDP-bound dimer is destabilized and dissociates, allowing GDP to be released. This makes the nucleotide pocket available for GTP binding, which initiates the recovery stroke. The G domain is now in position to dimerize with the next G-domain along the filament and performs more steps, each step reducing the membrane tube radius by approximately 1 nm.

Further Reading

• John R. Jimah, Jenny E. Hinshaw (2019): Structural Insights into the Mechanism of Dynamin Superfamily Proteins. Trends in Cell Biology 29(3), p257-273.
      DOI 10.1016/j.tcb.2018.11.003
  
  
• Katja Faelber, Martin Held, Song Gao, York Posor, Volker Haucke, Frank Noé, Oliver Daumke (2012): Structural Insights Into Dynamin-Mediated Membrane Fission, Structure, 20(10), 1621-8.
      DOI 10.1016/j.str.2012.08.028   

Structural references used in this project:

• : 3SNH
  Katja Faelber, York Posor, Song Gao, Martin Held, Yvette Roske, Dennis Schulze, Volker Haucke, Frank Noé, Oliver Daumke (2011), Crystal structure of nucleotide-free Dynamin, Nature, 477, 556-60.
      DOI 0.1038/nature10369
  
  
• : 2X2E
  Joshua S Chappie, Sharmistha Acharya, Marilyn Leonard, Sandra L Schmid, Fred Dyda (2010): G Domain dimerization controls Dynamin's assembly-stimulated GTPase activity, Nature, 465(7297), 435-40.
      DOI 10.1038/nature09032    
  
  
• : 3ZYC
  Joshua S Chappie, Jason A Mears, Shunming Fang, Marilyn Leonard, Sandra L Schmid, Ronald A Milligan, Jenny E Hinshaw, Fred Dyda (2011): A pseudoatomic model of the Dynamin polymer identifies a hydrolysis-dependent powerstroke, Cell, 147(1) , 209-22.
      DOI 10.1016/j.cell.2011.09.003    
  
  
• : 2DYN
  Kathryn M. Ferguson, Mark A. Lemmon, Joseph Schlessinger, Paul B. Sigler (1994): Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human Dynamin, Cell, 79/2), 199-209.
      DOI 10.1016/0092-8674(94)90190-2