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

RSC Advances ◽  
2017 ◽  
Vol 7 (37) ◽  
pp. 22741-22748 ◽  
Author(s):  
Nisha Bhattarai ◽  
Jeevan B. GC ◽  
Bernard S. Gerstman ◽  
Robert V. Stahelin ◽  
Prem P. Chapagain
Keyword(s):  
Plasma Membrane ◽  
Conformational Changes ◽  
Ebola Virus ◽  
Membrane Binding ◽  
Marburg Virus ◽  
Virus Protein ◽  
Membrane Association ◽  
Binding Interface

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.

scholarly journals Conformational Changes in Marburg Virus VP40 upon Plasma Membrane Association

2018 ◽  
Vol 114 (3) ◽  
pp. 459a
Author(s):  
Nisha Bhattarai ◽  
Prem P. Chapagain ◽  
Bernard S. Gerstman
Keyword(s):  
Plasma Membrane ◽  
Conformational Changes ◽  
Marburg Virus ◽  
Membrane Association

scholarly journals Interdomain salt-bridges in the Ebola virus protein VP40 and their role in domain association and plasma membrane localization

2016 ◽  
Vol 25 (9) ◽  
pp. 1648-1658 ◽  
Author(s):  
Jeevan B. GC ◽  
Kristen A. Johnson ◽  
Monica L. Husby ◽  
Cary T. Frick ◽  
Bernard S. Gerstman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ebola Virus ◽  
Membrane Localization ◽  
Virus Protein ◽  
Salt Bridges ◽  
Plasma Membrane Localization

scholarly journals Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6

2021 ◽  
Vol 5 (1) ◽  
pp. e202101149
Author(s):  
Yumiko Saijo-Hamano ◽  
Aalaa Alrahman Sherif ◽  
Ariel Pradipta ◽  
Miwa Sasai ◽  
Naoki Sakai ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Parasitophorous Vacuole ◽  
Membrane Binding ◽  
Structural Basis ◽  
In Silico Docking ◽  
Binding Interface ◽  
Dimerization Interface

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs.

scholarly journals Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein

2015 ◽  
Vol 89 (20) ◽  
pp. 10371-10382 ◽  
Author(s):  
Robert A. Dick ◽  
Siddhartha A. K. Datta ◽  
Hirsh Nanda ◽  
Xianyang Fang ◽  
Yi Wen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Rous Sarcoma Virus ◽  
Acyl Chain ◽  
Membrane Binding ◽  
Membrane Association ◽  
Gag Protein ◽  
Rous Sarcoma ◽  
Sarcoma Virus ◽  
Hiv 1

ABSTRACTPreviously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactionsin vitro. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particlesin vitro, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, which is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interactionin vitro, either by directly contacting acidic lipids or by promoting Gag multimerization.IMPORTANCERetroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our results show that RSV Gag is highly flexible and can adopt a folded-over conformation on a lipid bilayer, implicating both the N and C termini in membrane binding. In addition, binding of Gag to membranes is diminished when either terminal domain is truncated. RSV Gag membrane association is significantly less sensitive than HIV Gag membrane association to lipid acyl chain saturation. These findings shed light on Gag assembly and membrane binding, critical steps in the viral life cycle and an untapped target for antiretroviral drugs.

Ebola Virus Protein VP40 Binding to Sec24c for Transport to the Plasma Membrane

2021 ◽  
Author(s):  
Nisha Bhattarai ◽  
Elumalai Pavadai ◽  
Rudramani Pokhrel ◽  
Prabin Baral ◽  
Md Lokman Hossen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ebola Virus ◽  
Virus Protein

scholarly journals Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6

2021 ◽  
Author(s):  
Yumiko Saijo Hamano ◽  
Aalaa Alrahman Sherif ◽  
Ariel Pradipta ◽  
Miwa Sasai ◽  
Naoki Sakai ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Parasitophorous Vacuole ◽  
Membrane Binding ◽  
Structural Basis ◽  
In Silico Docking ◽  
Binding Interface ◽  
Toxoplasma Gondii Infection

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. It is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive due to lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP-binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs.

scholarly journals Mutation of Ebola Virus Matrix Protein Cysteine Residues Increases Binding to Phosphatidylserine through Increased Flexibility of a Lipid Binding Loop

2018 ◽  
Author(s):  
Kristen A. Johnson ◽  
Nisha Bhattarai ◽  
Melissa R. Budicini ◽  
Carolyn M. Shirey ◽  
Sarah Catherine B. Baker ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Membrane Lipids ◽  
Membrane Binding ◽  
Lipid Binding ◽  
Membrane Dynamics ◽  
Cysteine Residues ◽  
Virus Like Particles ◽  
Binding Loop

AbstractThe Ebola virus (EBOV) is a genetically simple negative sense RNA virus with only 7 genes yet it causes severe hemorrhagic fever in humans. The matrix protein VP40 of EBOV is the main driver of viral budding through binding to host plasma membrane lipids and formation of the filamentous, pleomorphic virus particles. To better understand this dynamic and complex process we have asked what the role of two highly conserved cysteine residues are in the C-terminal domain of VP40. Here we report that the mutation of Cys311to alanine increases VP40 membrane binding affinity for phosphatidylserine containing membranes. C311A has a significant increase in binding to PS compared to WT, has longer virus like particles, and displays evidence of increased budding. C314A also has an increase in PS binding compared to WT, however to a lesser extent. The double Cys mutant shares the phenotypes of the single mutants with increased binding to PS. Computational studies demonstrate these Cys residues, Cys311in particular, restrain a loop segment containing Lys residues that interact with the plasma membrane. Mutation of Cys311promotes membrane binding loop flexibility, alters internal VP40 H-bonding, and increases PS binding. To the best of our knowledge, this is the first evidence of mutations that increase VP40 affinity for biological membranes and the length of EBOV virus like particles. Together, our findings indicate these residues are important for membrane dynamics at the plasma membrane via the interaction with phosphatidylserine.

scholarly journals Cysteines Flanking the Internal Fusion Peptide Are Required for the Avian Sarcoma/Leukosis Virus Glycoprotein To Mediate the Lipid Mixing Stage of Fusion with High Efficiency

2008 ◽  
Vol 82 (6) ◽  
pp. 3131-3134 ◽  
Author(s):  
Sue E. Delos ◽  
Matthew B. Brecher ◽  
Zaoying Chen ◽  
Deborah C. Melder ◽  
Mark J. Federspiel ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Ebola Virus ◽  
High Efficiency ◽  
Fusion Peptide ◽  
Membrane Association ◽  
Virus Glycoprotein ◽  
Subtype A ◽  
Avian Sarcoma ◽  
Biphasic Profile ◽  
Virus Subtype

ABSTRACT We previously showed that the cysteines flanking the internal fusion peptide of the avian sarcoma/leukosis virus subtype A (ASLV-A) Env (EnvA) are important for infectivity and cell-cell fusion. Here we define the stage of fusion at which the cysteines are required. The flanking cysteines are dispensable for receptor-triggered membrane association but are required for the lipid mixing step of fusion, which, interestingly, displays a high pH onset and a biphasic profile. Second-site mutations that partially restore infection partially restore lipid mixing. These findings indicate that the cysteines flanking the internal fusion peptide of EnvA (and perhaps by analogy Ebola virus glycoprotein) are important for the foldback stage of the conformational changes that lead to membrane merger.

scholarly journals The Ebola virus protein VP40 hexamer enhances the clustering of PI(4,5)P2 lipids in the plasma membrane

2016 ◽  
Vol 18 (41) ◽  
pp. 28409-28417 ◽  
Author(s):  
Jeevan B. GC ◽  
Bernard S. Gerstman ◽  
Robert V. Stahelin ◽  
Prem P. Chapagain
Keyword(s):  
Plasma Membrane ◽  
Ebola Virus ◽  
Molecular Simulations ◽  
Virus Protein

Molecular simulations show that the VP40 hexamer strongly interacts with PI(4,5)P2 that results in an enhanced PI(4,5)P2 clustering.

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