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. 2009 Nov;5(11):e1000575.
doi: 10.1371/journal.pcbi.1000575. Epub 2009 Nov 20.

Computational model of membrane fission catalyzed by ESCRT-III

Gur Fabrikant  1 , Suman Lata, James D Riches, John A G Briggs, Winfried Weissenhorn, Michael M Kozlov
Affiliations

Computational model of membrane fission catalyzed by ESCRT-III

Gur Fabrikant et al. PLoS Comput Biol. 2009 Nov.

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Model for membrane budding and fission by the ESCRT-III sub-complexes.
A. Formation of the initial bud by CHMP4(Snf7) as suggested in ,. B. Self-assembly of CHMP2-CHMP3 nanotube with a dome-like end-cap. C. Fission of the neck and completion of the vesicle formation.
Figure 2
Figure 2. Lipid membrane attached to a protein dome – computed configuration and definitions.
(A) Fore-fission state: formula image- radius of the protein dome surface formula image - the neck radius, formula image- the attachment angle. (B) Post-fission state. The total membrane area formula image.
Figure 3
Figure 3. Dependence of the neck radius on the attachment angle.
The lines correspond to different values of the membrane area. (1) formula image; (2) formula image; (3) formula image.
Figure 4
Figure 4. Dependence of the total system energy on the attachment angle.
The lines correspond to different values of the membrane affinity to the protein dome surface formula image whose values are presented in the insert in mN/m, the total membrane area is formula image.
Figure 5
Figure 5. Phase diagrams describing different regimes of the system configurations in the fore-fission state.
The phase boundaries are determined by the characteristic values of the membrane affinity to the protein dome surface, formula image, formula image, and formula image. (A) The total energies of the narrow- and broad- neck configurations are represented by the lines 1 and 2, respectively. (B) The attachment angles in the narrow and broad neck configurations are represented by the lines 1 and 2, respectively, formula image (C) The characteristic affinities depending on the total membrane area formula image. The phase diagrams are divided into four regions corresponding to different regimes of the possible configurations of the system: (I) only broad neck; (II) stable broad neck and quasi-stable narrow neck; (III) stable narrow neck and quasi-stable broad neck; (IV) only narrow neck.
Figure 6
Figure 6. Comparison of the system energies in the fore- and post fission states for determination of the fission conditions.
Dashed lines are the energies of the post-fission state for different values of the modulus of the Gaussian curvature; solid lines (1) and (2) represent, respectively, the energies of the narrow and broad neck configurations of the fore-fission state, formula image.
Figure 7
Figure 7. The affinity needed for fission of the broad neck configuration to be energetically favorable depending on the modulus of the Gaussian curvature.
The total membrane area, formula image.
Figure 8
Figure 8. Imaging of the ESCRT-III (CHMP2A-CHMP3) assembly.
(A) Electron micrograph showing an ESCRT-III tubule terminating into a hemispherical end-cap structure. (B) The closed end of the tubule after image processing. (C) Extracted edge of the ESCRT-III end-cap. (D) Fit of the extracted edge into the image. (E) Fit of a circle into the edge profile. The methods and experimental details for (A)–(E) are presented in . (F) Cross sections of CHMP2A-CHMP3 end-capped tubular structures observed by cryo-electron tomography (see Materials and Methods). The images reveal the CHMP2A-CHMP3 protein layer and also the position of MBP proteins fused to the N-terminus of CHMP2A. The scale bar corresponds to a distance of 40nm.
See this image and copyright information in PMC

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