scholarly journals Polymorphism and Interactions of a Viral Fusion Peptide in a Compressed Lipid Monolayer

1999 ◽  
Vol 76 (6) ◽  
pp. 3167-3175 ◽  
Author(s):  
Gerhard Schwarz ◽  
Susanne E. Taylor
Keyword(s):  
Fusion Peptide ◽  
Lipid Monolayer ◽  
Viral Fusion

scholarly journals Condensation of the influenza viral fusion peptide alters membrane structure and water permeability

2021 ◽  
Author(s):  
Sourav Haldar ◽  
Amy Rice ◽  
Eric Wang ◽  
Paul S. Blank ◽  
Sergey A. Akimov ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Water Permeability ◽  
Membrane Structure ◽  
Pore Formation ◽  
Electron Tomography ◽  
Cellular Membrane ◽  
Fusion Peptide ◽  
Lipid Monolayer ◽  
Viral Fusion ◽  
Dynamics Simulations

To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out beyond a forest of viral spikes to embed into the target cellular membrane. Here we report that isolated FP of influenza virus are membrane active by themselves generating pores in giant unilamellar vesicles and thus potentially explain both influenza virus' hemolytic activity and structure in cryo-electron tomography. Molecular dynamics simulations of asymmetric bilayers with different numbers of FP in one leaflet show substantial peptide clustering. At the center of this peptide condensate a profound change in the membrane structure results in thinning, higher water permeability, and curvature. In effect, a hybrid bilayer forms locally with one lipid monolayer and one peptide monolayer. Membrane elastic theory predicts that the energy landscape becomes favorable for spontaneous pore formation in this novel structure, consistent with the inhibition of pore formation by cholesterol observed experimentally.

scholarly journals Functional Analysis of the Putative Fusion Domain of the Baculovirus Envelope Fusion Protein F

2004 ◽  
Vol 78 (13) ◽  
pp. 6946-6954 ◽  
Author(s):  
Marcel Westenberg ◽  
Frank Veenman ◽  
Els C. Roode ◽  
Rob W. Goldbach ◽  
Just M. Vlak ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Conformational Changes ◽  
Cellular Membrane ◽  
Fusion Peptide ◽  
Single Amino Acid ◽  
Viral Infectivity ◽  
Viral Fusion ◽  
F Protein ◽  
Group I ◽  
N Terminus

ABSTRACT Group II nucleopolyhedroviruses (NPVs), e.g., Spodoptera exigua MNPV, lack a GP64-like protein that is present in group I NPVs but have an unrelated envelope fusion protein named F. In contrast to GP64, the F protein has to be activated by a posttranslational cleavage mechanism to become fusogenic. In several vertebrate viral fusion proteins, the cleavage activation generates a new N terminus which forms the so-called fusion peptide. This fusion peptide inserts in the cellular membrane, thereby facilitating apposition of the viral and cellular membrane upon sequential conformational changes of the fusion protein. A similar peptide has been identified in NPV F proteins at the N terminus of the large membrane-anchored subunit F1. The role of individual amino acids in this putative fusion peptide on viral infectivity and propagation was studied by mutagenesis. Mutant F proteins with single amino acid changes as well as an F protein with a deleted putative fusion peptide were introduced in gp64-null Autographa californica MNPV budded viruses (BVs). None of the mutations analyzed had an major effect on the processing and incorporation of F proteins in the envelope of BVs. Only two mutants, one with a substitution for a hydrophobic residue (F152R) and one with a deleted putative fusion peptide, were completely unable to rescue the gp64-null mutant. Several nonconservative substitutions for other hydrophobic residues and the conserved lysine residue had only an effect on viral infectivity. In contrast to what was expected from vertebrate virus fusion peptides, alanine substitutions for glycines did not show any effect.

scholarly journals An Epitope of the Semliki Forest Virus Fusion Protein Exposed during Virus-Membrane Fusion

1999 ◽  
Vol 73 (12) ◽  
pp. 10029-10039 ◽  
Author(s):  
Anna Ahn ◽  
Matthew R. Klimjack ◽  
Prodyot K. Chatterjee ◽  
Margaret Kielian
Keyword(s):  
Membrane Fusion ◽  
Binding Site ◽  
Semliki Forest Virus ◽  
Fusion Reaction ◽  
Ph Dependence ◽  
Fusion Peptide ◽  
Endocytic Pathway ◽  
Spike Protein ◽  
Viral Fusion ◽  
Wide Range

ABSTRACT Semliki Forest virus (SFV) is an enveloped alphavirus that infects cells via a membrane fusion reaction triggered by acidic pH in the endocytic pathway. Fusion is mediated by the spike protein E1 subunit, an integral membrane protein that contains the viral fusion peptide and forms a stable homotrimer during fusion. We have characterized four monoclonal antibodies (MAbs) specific for the acid conformation of E1. These MAbs did not inhibit fusion, suggesting that they bind to an E1 region different from the fusion peptide. Competition analyses demonstrated that all four MAbs bound to spatially related sites on acid-treated virions or isolated spike proteins. To map the binding site, we selected for virus mutants resistant to one of the MAbs, E1a-1. One virus isolate, SFV 4-2, showed reduced binding of three acid-specific MAbs including E1a-1, while its binding of one acid-specific MAb as well as non-acid-specific MAbs to E1 and E2 was unchanged. The SFV 4-2 mutant was fully infectious, formed the E1 homotrimer, and had the wild-type pH dependence of infection. Sequence analysis demonstrated that the relevant mutation in SFV 4-2 was a change of E1 glycine 157 to arginine (G157R). Decreased binding of MAb E1a-1 was observed under a wide range of assay conditions, strongly suggesting that the E1 G157R mutation directly affects the MAb binding site. These data thus localize an E1 region that is normally hidden in the neutral pH structure and becomes exposed as part of the reorganization of the spike protein to its fusion-active conformation.

scholarly journals Identification and Characterization of the Putative Fusion Peptide of the Severe Acute Respiratory Syndrome-Associated Coronavirus Spike Protein

2005 ◽  
Vol 79 (11) ◽  
pp. 7195-7206 ◽  
Author(s):  
Bruno Sainz ◽  
Joshua M. Rausch ◽  
William R. Gallaher ◽  
Robert F. Garry ◽  
William C. Wimley
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Fusion Protein ◽  
Protein A ◽  
Fusion Peptide ◽  
Class I ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Viral Fusion Protein ◽  
Ww Ii ◽  
Heptad Repeats

ABSTRACT Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a newly identified member of the family Coronaviridae and poses a serious public health threat. Recent studies indicated that the SARS-CoV viral spike glycoprotein is a class I viral fusion protein. A fusion peptide present at the N-terminal region of class I viral fusion proteins is believed to initiate viral and cell membrane interactions and subsequent fusion. Although the SARS-CoV fusion protein heptad repeats have been well characterized, the fusion peptide has yet to be identified. Based on the conserved features of known viral fusion peptides and using Wimley and White interfacial hydrophobicity plots, we have identified two putative fusion peptides (SARSWW-I and SARSWW-II) at the N terminus of the SARS-CoV S2 subunit. Both peptides are hydrophobic and rich in alanine, glycine, and/or phenylalanine residues and contain a canonical fusion tripeptide along with a central proline residue. Only the SARSWW-I peptide strongly partitioned into the membranes of large unilamellar vesicles (LUV), adopting a β-sheet structure. Likewise, only SARSWW-I induced the fusion of LUV and caused membrane leakage of vesicle contents at peptide/lipid ratios of 1:50 and 1:100, respectively. The activity of this synthetic peptide appeared to be dependent on its amino acid (aa) sequence, as scrambling the peptide rendered it unable to partition into LUV, assume a defined secondary structure, or induce both fusion and leakage of LUV. Based on the activity of SARSWW-I, we propose that the hydrophobic stretch of 19 aa corresponding to residues 770 to 788 is a fusion peptide of the SARS-CoV S2 subunit.

scholarly journals A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Kwok-ho Lam ◽  
Zhuojun Guo ◽  
Nadja Krez ◽  
Tsutomu Matsui ◽  
Kay Perry ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Fusion Peptide ◽  
Molecular Switch ◽  
Membrane Insertion ◽  
Viral Fusion

Virus Membrane Fusion Proteins: Biological Machines that Undergo a Metamorphosis

2000 ◽  
Vol 20 (6) ◽  
pp. 597-612 ◽  
Author(s):  
Rebecca Ellis Dutch ◽  
Theodore S. Jardetzky ◽  
Robert A. Lamb
Keyword(s):  
Fusion Proteins ◽  
Ebola Virus ◽  
Transmembrane Domain ◽  
Coiled Coil ◽  
Fusion Peptide ◽  
Proteolytic Cleavage ◽  
Heptad Repeat ◽  
Viral Fusion ◽  
Hydrophobic Region ◽  
Viral Fusion Proteins

Fusion proteins from a group of widely disparate viruses, including the paramyxovirus F protein, the HIV and SIV gp160 proteins, the retroviral Env protein, the Ebola virus Gp, and the influenza virus haemagglutinin, share a number of common features. All contain multiple glycosylation sites, and must be trimeric and undergo proteolytic cleavage to be fusogenically active. Subsequent to proteolytic cleavage, the subunit containing the transmembrane domain in each case has an extremely hydrophobic region, termed the fusion peptide, or at near its newly generated N-terminus. In addition, all of these viral fusion proteins have 4–3 heptad repeat sequences near both the fusion peptide and the transmembrane domain. These regions have been demonstrated from a tight complex, in which the N-terminal heptad repeat forms a trimeric-coiled coil, with the C-terminal heptad repeat forming helical regions that buttress the coiled-coil in an anti-parallel manner. The significance of each of these structuralelements in the processing and function of these viral fusion proteins is discussed.

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