Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer

Bhattarai, Nisha; Jeevan, B.; Gerstman, Bernard S.; Stahelin, Robert V.; Chapagain, Prem P.

doi:10.1039/c7ra02940c

Cited by 15 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests to us that the CTD of mVP40 is rotated slightly about the CTD-NTD hinge into a position more similar to that of eVP40 when assembled in VP40 VLPs. A structural change in mVP40 in membrane binding has been proposed in prior simulation studies ( Bhattarai et al, 2017 ).…”

Section: Resultsmentioning

confidence: 93%

Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

Wan

Clarke

Norris

et al. 2020

eLife

View full text Add to dashboard Cite

Filoviruses such as Ebola and Marburg virus bud from the host membrane as enveloped virions. This process is achieved by the matrix protein VP40. When expressed alone, VP40 induces budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and generation of membrane curvature are intrinsic properties of VP40. There has been no direct information on the structure of VP40 matrix layers within viruses or virus-like particles. We present structures of Ebola and Marburg VP40 matrix layers in intact virus-like particles, and within intact Marburg viruses. VP40 dimers assemble extended chains via C-terminal domain interactions. These chains stack to form 2D matrix lattices below the membrane surface. These lattices form a patchwork assembly across the membrane and suggesting that assembly may begin at multiple points. Our observations define the structure and arrangement of the matrix protein layer that mediates formation of filovirus particles.

show abstract

Section: Resultsmentioning

confidence: 93%

Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

Wan

Clarke

Norris

et al. 2020

eLife

View full text Add to dashboard Cite

show abstract

“…As with eVP40, mVP40 has two loop regions in the CTD that contain cationic residues and form a lipid binding basic patch. As the dimer approaches the membrane, the number of contacts it makes with anionic lipids increases while contacts with the neutral hydrophobic acyl chains do not [ 19 ]. This is consistent with the lack of membrane penetration observed for mVP40 dimers in vitro [ 20 ] and in Cryo ET studies [ 9 ].…”

Section: Filovirus Assembly and Buddingmentioning

confidence: 99%

Lipid–protein interactions in virus assembly and budding from the host cell plasma membrane

Motsa

Stahelin

2021

Biochemical Society Transactions

View full text Add to dashboard Cite

Lipid enveloped viruses contain a lipid bilayer coat that protects their genome to help facilitate entry into the new host cell. This lipid bilayer comes from the host cell which they infect. After viral replication, the mature virion hijacks the host cell plasma membrane where it is then released to infect new cells. This process is facilitated by the interaction between phospholipids that make up the plasma membrane and specialized viral matrix proteins. This step in the viral lifecycle may represent a viable therapeutic strategy for small molecules that aim to block enveloped virus spread. In this review, we summarize the current knowledge on the role of plasma membrane lipid–protein interactions on viral assembly and budding.

show abstract

“…Modeller (Eswar et al, 2007) was used to model MeV-M using NiV-M as a template, and to fill the missing residues. The asymmetric lipid bilayer was built with POPC, POPE, POPS, PI(4,5)P2, PSM and CHOL in 41:7:3:3:22:20 ratios in the outer leaflet and in 10:35:15:13:4:20 ratios in the inner leaflet (Bhattarai et al, 2017;Gc et al, 2016Gc et al, , 2017van Meer et al, 2008;Zachowski, 1993), with 205 total lipids in upper leaflet and 208 in the lower leaflet. Each system was neutralized by 0.15 mM NaCl and solvated with TIP3P water model.…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Molecular assembly of measles and Nipah virus: specific lipid binding drives conformational change and matrix polymerization

Norris

Husby²,

Kiosses

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at the plasma membrane. Using X-ray crystallography, electron microscopy, and molecular dynamics we demonstrate that PI(4,5)P2 binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly.

show abstract

Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer

Abstract: The membrane binding interface of the Marburg virus protein mVP40 dimer differs from that of the Ebola virus eVP40 dimer but membrane binding allows conformational changes in mVP40 that makes it structurally similar to the eVP40 dimer.

Cited by 15 publications

References 47 publications

Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

Lipid–protein interactions in virus assembly and budding from the host cell plasma membrane

Molecular assembly of measles and Nipah virus: specific lipid binding drives conformational change and matrix polymerization

Contact Info

Product

Resources

About