Dynamin-superfamily proteins are mechanochemical, membrane-remodeling proteins, which regulate many fusion, fission, and trafficking events in the cell. The founding member, dynamin, mediates endocytosis, synaptic vesicle recycling, and membrane trafficking. It does so by assembling around the necks of budding vesicles as a helical polymer which upon GTP hydrolysis, undergoes a significant constriction eventually resulting in membrane fission. Dynamin dysfunction has been associated with neuronal conditions including: epilepsy, Charcot-Marie-Tooth, centronuclear myopathy, hereditary spastic paraplegia, and cancer. We have resolved dozens of dynamin-1 helical assemblies in the presence of various native lipid conditions and nucleotide mimicking states using cryo-electron microscopy. This array of structures illuminates potential intermediates in the landscape of progressively narrowing helical assemblies of the dynamin-1 polymer, from the apo state to the super-constricted state. Advancements in image processing reveal novel interfaces, including contacts in the pleckstrin homology (PH) and GTPase domains, which help explain dynamin’s mode of interaction during membrane remodeling. Future nuclear magnetic resonance, mutagenesis, and cellular assays hope to better elucidate dynamin’s mechanism of membrane fission and its disease relevance.
Nyenhuis et al. (Sun,) studied this question.