Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

McCullough, John; Frost, Adam; Sundquist, Wesley I.

doi:10.1146/annurev-cellbio-100616-060600

Cited by 231 publications

(286 citation statements)

References 137 publications

(232 reference statements)

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“…Although CHMP4 assembles on flat membranes 30,60 , it seems to prefer negative membrane curvature for interaction 61 . Thus, the CHMP2B and CHMP2A+CHMP3 membrane binding observed here has produced assemblies that are different from ESCRT-III assemblies observed in vitro 62,63 lacking spontaneous curvature and/or being too elastic to deform membranes.…”

Section: Discussionmentioning

confidence: 55%

The ESCRT-III Isoforms CHMP2A And CHMP2B Display Different Effects On Membranes Upon Polymerization

Alqabandi

Franceschi

Miguet

et al. 2019

Preprint

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ESCRT-III proteins are involved in many membrane remodeling processes including multivesicular body biogenesis as first discovered in yeast. In humans, CHMP2 exists as two potential isoforms, CHMP2A and CHMP2B, but their physical characteristics have not been compared yet. Here, we use a combination of technics on biomimetic systems and purified proteins to study their affinity and effects on membranes. We establish that CHMP2B binding is enhanced in the presence of PI(4,5)P2 lipids. In contrast, CHMP2A does not display lipid specificity and requires CHMP3 for binding significantly to membranes. On the micrometer scale and at moderate bulk concentrations, CHMP2B forms a reticular structure on membranes whereas CHMP2A (+CHMP3) binds homogeneously. Eventually, CHMP2A and CHMP2B unexpectedly induce different mechanical effects to membranes: CHMP2B strongly rigidifies them while CHMP2A (+CHMP3) has no significant effect. Altogether, we conclude that CHMP2B and CHMP2A cannot be considered as isoforms and might thus contribute differently to membrane remodeling processes.

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Section: Discussionmentioning

confidence: 55%

The ESCRT-III Isoforms CHMP2A And CHMP2B Display Different Effects On Membranes Upon Polymerization

Alqabandi

Franceschi

Miguet

et al. 2019

Preprint

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“…However, we note that the region of pUL51 immediately following helix α2 is predicted to be helical ( Fig. S2) and in ESCRT-III structures helix α3 is known to be mobile, adopting both 'closed' and 'open' (extended) conformations (33). The polymerization of CHMP4B is known to be regulated by association with CC2D1A in humans (34) and Lgd in flies (37).…”

Section: Discussionmentioning

confidence: 97%

“…Of the proteins identified by structure-based searches, the similarity to human CHMP4B, a component of the ESCRT-III membrane-remodeling machinery, is particularly notable given the role of pUL51 and homologues in stimulating virus wrapping (6,13,14,20). CHMP4B and homologues are required for the efficient fusion of membrane leaflets during vesicle budding into organelle lumens, cytokinetic abscission, nuclear envelope closure, and budding of some enveloped viruses (33). Helices α1 and α2 of pUL51 superpose onto human CHMP4B (34) with 1.2 Å root-mean-squared deviation across 59 C α atoms (Fig.…”

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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“…Even micron-scale punctures caused by lasers undergo slow repair (Denais et al, 2016;Penfield et al, 2018;Halfmann et al, 2019). Given the evidence that the ESCRT-III spiral filament (VPS-32/Snf7/CHMP4B) resolves holes of ~30-50 nm in diameter (Wollert and Hurley, 2010;McCullough et al, 2018;Olmos et al, 2015;, mechanisms must exist to narrow large membrane holes in interphase NE ruptures and during NE reformation before ESCRT-III acts. ESCRTmachinery may have a direct role in the constriction of larger holes.…”

Section: Introductionmentioning

confidence: 99%

“…ESCRTmachinery may have a direct role in the constriction of larger holes. In fact, ESCRT-III components line the >1 μm wide cytokinetic bridge (Elia et al, 2011;Guizetti et al, 2011), although exactly how constriction occurs at the site of abscission remains unclear (McCullough et al, 2018;Henne et al, 2013). The NE-specific adaptors for ESCRTs, CHMP7 and LEM2/LEM-2, may contribute to constricting large NE openings, although currently evidence for this does not exist.…”

Section: Introductionmentioning

confidence: 99%

Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure

Penfield

Shankar

Szentgyörgyi

et al. 2019

Preprint

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The nuclear permeability barrier depends on closure of holes in the nuclear envelope (NE). Here, we use meiotic C. elegans oocytes to demonstrate that local control of glycerophospholipid synthesis by CNEP-1/CTDNEP1 regulates the insertion of ER sheets into NE holes and functions independently of ESCRT-III to ensure NE closure.Deletion of CNEP-1 causes excess incorporation of ER membranes into NE holes and a defective NE permeability barrier. ESCRT-III components accumulate at the NE opening surrounding the meiotic spindle, and loss of NE adaptors for ESCRT-III exacerbates NE sealing defects in cnep-1 mutants. Limiting ER sheet production by restoring glycerophospholipid synthesis in cnep-1 mutants rescued NE permeability defects. 3D analysis showed that membrane sheets feed into and narrow NE holes occluded by meiotic spindle microtubules supporting a role for ER sheet insertion in NE closure.Thus, feeding of ER sheets into NE holes must be coordinated with production of ER sheets near the NE to promote NE closure.

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Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

Cited by 231 publications

References 137 publications

The ESCRT-III Isoforms CHMP2A And CHMP2B Display Different Effects On Membranes Upon Polymerization

The ESCRT-III Isoforms CHMP2A And CHMP2B Display Different Effects On Membranes Upon Polymerization

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

Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure

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