Membrane constriction by Dynamin
Membrane constriction by Dynamin
Katja Faelber, Jeffrey Noel and Oliver Daumke - Max Delbrück Center for Molecular Medicine (MDC), Berlin (https://www.mdc-berlin.de/daumke)
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.
Structural References:
3SNH (http://www.rcsb.org/structure/3SNH) - Faelber et al. (2011), Nature 477: 556 (https://www.ncbi.nlm.nih.gov/pubmed/2...
2X2E (https://www.rcsb.org/structure/2X2F) - Chappie et al. (2010), Nature 465:435 (https://www.ncbi.nlm.nih.gov/pubmed/2...
3ZYC (https://www.rcsb.org/structure/3zyc) - Chappie et al. (2011), Cell 147:209 (https://www.ncbi.nlm.nih.gov/pubmed/1...
2DYN (http://www.rcsb.org/structure/2DYN) - Ferguson (1994), Cell 79:199 (https://www.ncbi.nlm.nih.gov/pubmed/7...)
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Molecular Animation by Erik Werner, RNS Berlin
further information at http://www.rns.berlin