VPS4 triggers constriction and cleavage of ESCRT-III helical filaments

Maity, Sourav; Caillat, Christophe; Miguet, Nolwenn; Sulbarán, Guidenn; Effantin, Grégory; Schoehn, Guy; Roos, Wouter H.; Weissenhorn, Winfríed

doi:10.1126/sciadv.aau7198

Cited by 90 publications

(96 citation statements)

References 58 publications

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“…This analysis aligns well with the recent experiments byGoliand et al, in which the geometry change between a ring and a spiral ESCRT-III filament, caused by Vps4, is suggested to drive the constriction of the intercellular membrane bridge between two dividing cells(27). Similarly, Maity et al have recently shown that Vps4 causes changes in the helical radius of ESCRT-III helical filaments in vitro, again suggesting that a geometry change of the filament is underlying ESCRT-III-mediated membrane remodelling(37). Finally,Pfitzner et al have recently demonstrated that Vps4 ATP-ase promotes sequential changes in the composition of various ESCRT-III proteins within the filament, which is directly coupled to the filament's ability to remodel the membrane(28).…”

supporting

confidence: 91%

Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission

Harker-Kirschneck

Baum

Šarić

2019

Preprint

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ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct to other cytoskeletal filaments, ESCRT-III filaments do not consume energy, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling. Here we present a minimal coarse-grained model that that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments induces transitions between a flat spiral and a 3D helix to drive membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles. The mechanistic principles revealed here will enable manipulation of ESCRT-III-driven processes in cells and in guiding the engineering of synthetic membrane-sculpting systems.

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supporting

confidence: 91%

Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission

Harker-Kirschneck

Baum

Šarić

2019

Preprint

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“…The HS-AFM experiments on lipid bilayers were performed using SLBs composed of 60% DOPC, 30% DOPS, and 10% PI(4,5)P2. The SLBs were formed by incubating LUVs on top of freshly cleaved mica, as described in 39 . Briefly, LUVs were thawed at room temperature and diluted to a concentration of 0.2 mg/ml in buffer (25mM Tris, pH 7.4, 50mM NaCl).…”

Section: Surface Preparation For Hs-afmmentioning

confidence: 99%

“…Common to all ESCRT-mediated processes is the strict requirement of VPS4 that not only recycles ESCRT-III 36 , but actively remodels the polymers in vivo 14,37 and in vitro 38,39 . Vps4/VPS4 ESCRT-III remodeling seems to be critical to complete release 14,40,41 .…”

Section: Introductionmentioning

confidence: 99%

Human ESCRT-III Polymers Assemble on Positively Curved Membranes and Induce Helical Membrane Tube Formation

Bertin

Franceschi

Mora

et al. 2019

Preprint

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Endosomal sorting complexes required for transport-III (ESCRT-III) are thought to assemble in vivo inside membrane structures with a negative Gaussian curvature. How membrane shape influences ESCRT-III polymerization and conversely how ESCRT-III polymers shape membranes is still unclear. Here, we used human core ESCRT-III proteins, CHMP4B, CHMP2A, CHMP2B and CHMP3 to address this issue in vitro by combining membrane nanotube pulling experiments, cryo-electron microscopy, cryo-electron tomography and highspeed AFM. We show that CHMP4B filaments bind preferentially to flat membranes or to membrane tubes with a positive mean curvature. Both CHMP2B and CHMP2A/CHMP3 assemble on positively curved membrane tubes, the latter winding around the tubes. Although combinations of CHMP4B/CHMP2B and CHMP4B/CHMP2A/CHMP3 are recruited to the neck of pulled membrane tubes, they also reshape large unilamellar vesicles into helical membrane tubes with a pipe surface shape. Sub-tomogram averaging reveals that the filaments assemble parallel to the tube axis with some local perpendicular connections, highlighting the particular mechanical stresses imposed by ESCRT-III to stabilize the corkscrew-like membrane architecture. Our results thus underline the versatile membrane remodeling activity of ESCRT-III that may be a general feature of ESCRT-III required for all or selected cellular membrane remodeling processes.

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“…Activity of ESCRT-III components and VPS4, the AAA-ATPase that promotes fusion and dissociates ESCRT-III (33,38), are known to be required for efficient assembly of HSV-1 (39,40). However, a recent study of HCMV identified that neither VPS4 nor mammalian ESCRT-III components CHMP4B or CHMP6 are required for assembly, and the authors hypothesized that pUL71 may act as a viral ESCRT-III homologue (41).…”

Section: Discussionmentioning

confidence: 99%

Structure of herpes simplex virus pUL7:pUL51, a conserved complex required for efficient herpesvirus assembly

Butt

Owen

Jeffries³

et al. 2019

Preprint

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Herpesviruses are an ancient family of highly-prevalent human and animal pathogens that acquire their membrane envelopes in the cytoplasm of infected cells. While multiple conserved viral proteins are known to be required for efficient herpesvirus production, many of these proteins lack identifiable structural homologues and the molecular details of herpesvirus assembly remain unclear. We have characterized the complex of assembly proteins pUL7 and pUL51 from herpes simplex virus (HSV)-1, an α-herpesvirus, using multi-angle light scattering and small-angle X-ray scattering with chemical crosslinking. HSV-1 pUL7 and pUL51 form a stable 1:2 complex that is capable of higher-order oligomerization in solution. We solved the crystal structure of this complex, revealing a core heterodimer comprising pUL7 bound to residues 41-125 of pUL51. While pUL7 adopts a previously-unseen compact fold, the extended helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. We demonstrate that the interaction between pUL7 and pUL51 homologues is conserved across human α-, β-and γ-herpesviruses, as is their association with trans-Golgi membranes in cultured cells. However, pUL7 and pUL51 homologues do not form complexes with their respective partners from different virus families, suggesting that the molecular details of the interaction interface have diverged. Our results demonstrate that the pUL7:pUL51 complex is conserved across the herpesviruses and provide a structural framework for understanding its role in herpesvirus assembly. Significance StatementHerpesviruses are extremely common human pathogens that cause diseases ranging from cold sores to cancer. Herpesvirus acquire their membrane envelope in the cytoplasm via a conserved pathway, the molecular details of which remain unclear. We have solved the structure of a complex between herpes simplex virus (HSV)-1 proteins pUL7 and pUL51, two proteins that are required for efficient HSV-1 assembly. We show that formation of this complex is conserved across distantly-related human herpesviruses, as is the association of these homologues with cellular membranes that are used for virion assembly. While pUL7 adopts a previously-unseen fold, pUL51 resembles key cellular membrane-remodeling complex components, suggesting that the pUL7:pUL51 complex may play a direct role in deforming membranes to promote virion assembly.

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VPS4 triggers constriction and cleavage of ESCRT-III helical filaments

Cited by 90 publications

References 58 publications

Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission

Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission

Human ESCRT-III Polymers Assemble on Positively Curved Membranes and Induce Helical Membrane Tube Formation

Structure of herpes simplex virus pUL7:pUL51, a conserved complex required for efficient herpesvirus assembly

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