Dynamin facilitates endocytosis by severing invaginating vesicles through its GTPase activity. Dynamin-mediated endocytosis involves three steps: helical polymer formation around the necks of invaginating pits, membrane constriction of the necks upon GTP binding, and membrane fission leading to vesicle release via GTP hydrolysis. Using cryo-EM with native-like lipids, we captured intermediates of dynamin-1 helical assembly, revealing a novel interface in the PH domain. The array of structures illuminates potential intermediates in the assembly of the dynamin-1 helical polymer, from the apo state to the super-constricted state. Advancements in image processing reveal a novel interface and loops which have not been observed previously within the landscape of dynamin-1 helical assemblies. In particular, we observe contacts in the Pleckstrin Homology (PH) domains, which help explain dynamin’s mode of interaction during membrane remodeling. This work provides critical mechanistic insights into the molecular processes driving dynamin-mediated membrane fission during endocytosis, elucidating the conformational changes and lipid interactions essential for endocytic vesicle scission. Future studies will further elucidate its fission mechanism and disease relevance.
Kundu et al. (2026) studied this question.