Structural characterization and membrane binding properties of the matrix protein VP40 of ebola virus

Ruigrok, Rob W.H.; Schoehn, Guy; Dessen, Andréa; Forest, Éric; Volchkov, Viktor E.; Dolnik, Olga; Klenk, Hans‐Dieter; Weissenhorn, Winfríed

doi:10.1006/jmbi.2000.3822

Cited by 148 publications

(211 citation statements)

References 58 publications

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“…As postulated for other M-proteins (20,29), the basic face of the BDV-M tetramer, interspersed with surface exposed aliphatic and aromatic residues, could facilitate membrane targeting and/or binding, consistent with membrane binding capabilities of the BDV-M tetramer (16). VP40 membrane binding is affected by the C-terminal domains in the hexameric state (9,33) in an as-yet-unknown manner.…”

Section: Discussionmentioning

confidence: 62%

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Neumann¹,

Lieber²,

Meyer³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 62%

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Neumann¹,

Lieber²,

Meyer³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…1 C). Because the binding of M to cell membranes is thought to be mediated largely by electrostatic contacts (12,28), this region provides a mechanism by which the protein is able to associate with negatively charged host membranes. Comparison of the electrostatic surface of M 254 with VP40 is hampered by the fact that in the latter the linker region is not modeled.…”

Section: Resultsmentioning

confidence: 99%

“…A number of matrix-like proteins are known to bind membranes or lipid vesicles in vitro, most likely through a combination of hydrophobic and electrostatic interactions (12)(13)(14). Expression of certain Ms in eukaryotic cells in the absence of other viral proteins can induce formation of virus-like particles (VLPs).…”

mentioning

confidence: 99%

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Money

McPhee²,

Mosely³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The matrix protein (M) of respiratory syncytial virus (RSV), the prototype viral member of the Pneumovirinae (family Paramyxoviridae, order Mononegavirales), has been crystallized and the structure determined to a resolution of 1.6 Å. The structure comprises 2 compact ␤-rich domains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering Ϸ600 Å 2 can be resolved. This unusually large patch of positive surface potential spans both domains and the linker, and provides a mechanism for driving the interaction of the protein with a negatively-charged membrane surface or other virion components such as the nucleocapsid. This patch is complemented by regions of high hydrophobicity and a striking planar arrangement of tyrosine residues encircling the C-terminal domain. Comparison of the RSV M sequence with other members of the Pneumovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the majority of viral species-specific differences occurring in the N-terminal domain.CD ͉ crystal structure ͉ respiratory syncytial virus ͉ sequence alignment R espiratory syncytial virus (RSV) is the prototype member of the Pneumovirinae, a subfamily of the Paramyxoviridae (order Mononegavirales). Morphologically, the extracellular virion consists of a lipid bilayer envelope, within which are embedded 3 glycoproteins, 2 of which (F and G) are important in cell attachment and viral entry into target cells. The third, the SH protein, contributes to pathology in the host (1). Internally, virions contain helical nucleocapsids that consist of N protein tightly bound to the negative-sense nonsegmented genomic RNA. The nucleocapsid in turn is associated with components of the viral RNA-dependent RNA polymerase (L, P, M2-1, and M2-2 proteins), forming the holo-nucleocapsid (2-4). Between the holo-nucleocapsid and the outer envelope there is a layer of matrix protein (M), which is associated peripherally with the membrane (5). The other family members of the Mononegavirales (Rhabdoviridae, Filoviridae, and Bornaviridae) all subscribe to this basic arrangement of the virion, although the overall morphology can vary between the families. For example, Paramyxoviridae virions are pleiomorphic, whereas the Rhabdoviridae have a regular bullet shape structure, and the Filoviridae have a more filamentous shape. Extracellular RSV virions form by a budding process that occurs at the plasma membrane within specialized lipid domains (5, 6) and M appears to drive the final assembly process, which is the incorporation of the holo-nucleocapsid and initiation of the budding process (7,8). Before budding, there is a coordinated assembly of viral components; and it is evident that the glycoproteins and M proteins are important determinants of the location on the plasma membrane at which the virus buds (9). It is also possible that the interaction between M and the glycoproteins, possibly mediat...

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“…The first X-ray structure of VP40 (17) demonstrated that VP40 harbored an Nterminal domain that has been shown to mediate VP40 oligomerization (1,7,18) and a C-terminal domain that can interact with anionic membranes (1,13,(19)(20)(21)(22). Additionally, VP40 harbors a ~43 amino acid long Nterminal region that has not been resolved in crystal structures.…”

Section: Introductionmentioning

confidence: 99%

“…While the molecular basis of VP40 association with the anionic inner leaflet of the PM is unknown, it is clear that both electrostatic (19) and hydrophobic interactions (10,13) play an important role. Hydrophobic residues in the Cterminal domain are critical to localization, membrane penetration, and budding (13) while interactions with phosphatidylserine (PS) have been shown to be important for association with lipid vesicles in vitro (19,20,22,27) and budding from the plasma membrane of mammalian cells (27).…”

Section: Introductionmentioning

confidence: 99%

A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix VP40 protein control its interactions with phosphatidylserine

Vecchio

Frick

Jeevan

et al. 2018

Journal of Biological Chemistry

134

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Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causeshemorrhagic fever with a high fatality rate. Viral protein 40 (VP40) is the major EBOV matrix protein and regulates viral budding from the plasma membrane. VP40 is a transformer/morpheein that can structurally rearrange its native homodimer into either a hexameric filament that facilitates viral budding or a RNA-binding octameric ring that regulates viral transcription. VP40 associates with plasma-membrane lipids such as phosphatidylserine (PS), and this association is critical to budding from the host cell. However, it is poorly understood how different VP40 structures interact with PS, what essential residues are involved in this association, and whether VP40 has true selectivity for PS among different glycerophospholipid headgroups. In this study, we used lipid-binding assays, MD simulations, and cellular imaging to investigate the molecular basis of VP40-PS interactions and to determine whether different VP40 structures (i.e. monomer, dimer, and octamer) can interact with PScontaining membranes. Results from quantitative analysis indicated that VP40 associates with PS vesicles via a cationic patch in the C-terminal domain (Lys-224, 225 and Lys-274, 275). Substitutions of these residues with alanine reduced PSvesicle binding by >40-fold and abrogated VP40 localization to the plasma membrane. Dimeric VP40 had 2-fold greater affinity for PS-containing membranes than the monomer, whereas binding of the VP40 octameric ring was reduced by nearly 10-fold. Taken together, these results suggest http://www.jbc.org/cgi

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Structural characterization and membrane binding properties of the matrix protein VP40 of ebola virus

Cited by 148 publications

References 58 publications

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix VP40 protein control its interactions with phosphatidylserine

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