Computational Model of Membrane Fission Catalyzed by ESCRT-III

TLDR

ESCRT‑III proteins drive membrane fission in multivesicular body formation, viral budding, and cytokinesis. The study proposes and analyzes a novel mechanism whereby CHMP2–CHMP3 complexes self‑assemble into dome‑like structures that mediate membrane fission. The model shows that dome formation attaches to the membrane, narrows the neck, accumulates elastic stress, and requires a specific protein‑membrane binding energy to trigger fission. The calculations predict a high fission efficiency for CHMP2–CHMP3 complexes, which is corroborated by electron‑tomography imaging of their assemblies in vitro.

Abstract

ESCRT-III proteins catalyze membrane fission during multi vesicular body biogenesis, budding of some enveloped viruses and cell division. We suggest and analyze a novel mechanism of membrane fission by the mammalian ESCRT-III subunits CHMP2 and CHMP3. We propose that the CHMP2-CHMP3 complexes self-assemble into hemi-spherical dome-like structures within the necks of the initial membrane buds generated by CHMP4 filaments. The dome formation is accompanied by the membrane attachment to the dome surface, which drives narrowing of the membrane neck and accumulation of the elastic stresses leading, ultimately, to the neck fission. Based on the bending elastic model of lipid bilayers, we determine the degree of the membrane attachment to the dome enabling the neck fission and compute the required values of the protein-membrane binding energy. We estimate the feasible values of this energy and predict a high efficiency for the CHMP2-CHMP3 complexes in mediating membrane fission. We support the computational model by electron tomography imaging of CHMP2-CHMP3 assemblies in vitro. We predict a high efficiency for the CHMP2-CHMP3 complexes in mediating membrane fission.