Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

14-POS Board 5 DYNAMIN MEDIATES FISSION BY CONSTRICTION UNTIL NOT ONLY HEMI FISSION BUT ALSO FULL-FISSION

Ammar Mohseni 1 ; Ling-Gang Wu 1 ; 1 National Institutes of Health, NINDS, Bethesda, MD, USA

Membrane fission is a vital intracellular process in the biological systems that involves in various functions such as cell division, mitochondrial splitting, endocytosis, and intracellular trafficking. As the most popular fission enzyme, The GTPase dynamin may spontaneously polymerize into a helical spiral polymer around the budding vesicle’s neck and mediate scission of the neck hydrolyzing Guanosine triphosphate (GTP). However, the exact mechanistic role of dynamin in membrane fission is not well understood and debated. Several hypotheses have been proposed to account for dynamin-mediated fission: 1) constrictase/ratchet model in which membrane neck is constricted by dynamin the neck size reaches 3-4 nm, at which hemi-fission and then full-fission takes place spontaneously, 2) disassembling model in which dynamin constricts the membrane by assembling around of the neck, then disassembly leads to fission. Here, we used coarse grained (CG) molecular dynamics (MD) simulation to study dynamin-mediated fission. the helical form of dynamin 1 polymer was constructed based on the previously published cryo electron microscopy data in constricted and super-constricted states. To accelerate the MD simulation, the Pleckstrin Homology (PH) domain (lipid binding domain) of the dynamin 1 was kept in the helical form and other regions were removed. A W-shape DOPS membrane was created, with dynamin helix surrounding the neck. Pulling force is applied to move dynamin around the membrane tube to constrict it. We found that dynamin helix has to constrict the neck until the neck inner diameter reach 0 nm to mediate hemi-fission. Furthermore, dynamin helix constriction is needed to mediate hemi-to-full fission. These results suggest that dynamin helix constricts the membrane neck until full-fission occurs.

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