scholarly journals Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins

2005 ◽  
Vol 169 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Elena Zaitseva ◽  
Aditya Mittal ◽  
Diane E. Griffin ◽  
Leonid V. Chernomordik
Keyword(s):  
Influenza Virus ◽  
Fusion Proteins ◽  
Low Ph ◽  
Viral Fusion ◽  
Fusion Reactions ◽  
Influenza Virus Hemagglutinin ◽  
Viral Fusion Proteins ◽  
The Difference ◽  
Fusion Pores ◽  
Specific Inhibitors

Viral fusion proteins of classes I and II differ radically in their initial structures but refold toward similar conformations upon activation. Do fusion pathways mediated by alphavirus E1 and influenza virus hemagglutinin (HA) that exemplify classes II and I differ to reflect the difference in their initial conformations, or concur to reflect the similarity in the final conformations? Here, we dissected the pathway of low pH–triggered E1-mediated cell–cell fusion by reducing the numbers of activated E1 proteins and by blocking different fusion stages with specific inhibitors. The discovered progression from transient hemifusion to small, and then expanding, fusion pores upon an increase in the number of activated fusion proteins parallels that established for HA-mediated fusion. We conclude that proteins as different as E1 and HA drive fusion through strikingly similar membrane intermediates, with the most energy-intensive stages following rather than preceding hemifusion. We propose that fusion reactions catalyzed by all proteins of both classes follow a similar pathway.

scholarly journals Mechanism of membrane fusion induced by vesicular stomatitis virus G protein

2016 ◽  
Vol 114 (1) ◽  
pp. E28-E36 ◽  
Author(s):  
Irene S. Kim ◽  
Simon Jenni ◽  
Megan L. Stanifer ◽  
Eatai Roth ◽  
Sean P. J. Whelan ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
G Protein ◽  
Vesicular Stomatitis Virus ◽  
Fusion Proteins ◽  
Low Ph ◽  
Viral Fusion ◽  
Protein Fusion ◽  
West Nile ◽  
Vesicular Stomatitis ◽  
Viral Fusion Proteins

The glycoproteins (G proteins) of vesicular stomatitis virus (VSV) and related rhabdoviruses (e.g., rabies virus) mediate both cell attachment and membrane fusion. The reversibility of their fusogenic conformational transitions differentiates them from many other low-pH-induced viral fusion proteins. We report single-virion fusion experiments, using methods developed in previous publications to probe fusion of influenza and West Nile viruses. We show that a three-stage model fits VSV single-particle fusion kinetics: (i) reversible, pH-dependent, G-protein conformational change from the known prefusion conformation to an extended, monomeric intermediate; (ii) reversible trimerization and clustering of the G-protein fusion loops, leading to an extended intermediate that inserts the fusion loops into the target-cell membrane; and (iii) folding back of a cluster of extended trimers into their postfusion conformations, bringing together the viral and cellular membranes. From simulations of the kinetic data, we conclude that the critical number of G-protein trimers required to overcome membrane resistance is 3 to 5, within a contact zone between the virus and the target membrane of 30 to 50 trimers. This sequence of conformational events is similar to those shown to describe fusion by influenza virus hemagglutinin (a “class I” fusogen) and West Nile virus envelope protein (“class II”). Our study of VSV now extends this description to “class III” viral fusion proteins, showing that reversibility of the low-pH-induced transition and architectural differences in the fusion proteins themselves do not change the basic mechanism by which they catalyze membrane fusion.

scholarly journals Sequential Roles of Receptor Binding and Low pH in Forming Prehairpin and Hairpin Conformations of a Retroviral Envelope Glycoprotein

2004 ◽  
Vol 78 (15) ◽  
pp. 8201-8209 ◽  
Author(s):  
Shutoku Matsuyama ◽  
Sue Ellen Delos ◽  
Judith M. White
Keyword(s):  
Fusion Proteins ◽  
Transmembrane Domain ◽  
Fusion Peptide ◽  
Low Ph ◽  
Class I ◽  
Viral Fusion ◽  
Conformational States ◽  
Helix Bundle ◽  
Subsequent Exposure ◽  
Viral Fusion Proteins

ABSTRACT A general model has been proposed for the fusion mechanisms of class I viral fusion proteins. According to this model a metastable trimer, anchored in the viral membrane through its transmembrane domain, transits to a trimeric prehairpin intermediate, anchored at its opposite end in the target membrane through its fusion peptide. A subsequent refolding event creates a trimer of hairpins (often termed a six-helix bundle) in which the previously well-separated transmembrane domain and fusion peptide (and their attached membranes) are brought together, thereby driving membrane fusion. While there is ample biochemical and structural information on the trimer-of-hairpins conformation of class I viral fusion proteins, less is known about intermediate states between native metastable trimers and the final trimer of hairpins. In this study we analyzed conformational states of the transmembrane subunit (TM), the fusion subunit, of the Env glycoprotein of the subtype A avian sarcoma and leukosis virus (ASLV-A). By analyzing forms of EnvA TM on mildly denaturing sodium dodecyl sulfate gels we identified five conformational states of EnvA TM. Following interaction of virions with a soluble form of the ASLV-A receptor at 37°C, the metastable form of EnvA TM (which migrates at 37 kDa) transits to a 70-kDa and then to a 150-kDa species. Following subsequent exposure to a low pH (or an elevated temperature or the fusion promoting agent chlorpromazine), an additional set of bands at >150 kDa, and then a final band at 100 kDa, forms. Both an EnvA C-helix peptide (which inhibits virus fusion and infectivity) and the fusion-inhibitory agent lysophosphatidylcholine inhibit the formation of the >150- and 100-kDa bands. Our data are consistent with the 70- and 150-kDa bands representing precursor and fully formed prehairpin conformations of EnvA TM. Our data are also consistent with the >150-kDa bands representing higher-order oligomers of EnvA TM and with the 100-kDa band representing the fully formed six-helix bundle. In addition to resolving fusion-relevant conformational intermediates of EnvA TM, our data are compatible with a model in which the EnvA protein is activated by its receptor (at neutral pH and a temperature greater than or equal to room temperature) to form prehairpin conformations of EnvA TM, and in which subsequent exposure to a low pH is required to stabilize the final six-helix bundle, which drives a later stage of fusion.

scholarly journals Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion

2005 ◽  
Vol 171 (1) ◽  
pp. 111-120 ◽  
Author(s):  
Maofu Liao ◽  
Margaret Kielian
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Class Ii ◽  
Dominant Negative ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Fusion Reactions ◽  
Dominant Negative Inhibitor ◽  
Viral Fusion Proteins ◽  
Domain Iii

Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. We demonstrate that exogenous domain III can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and infection. Domain III binds stably to the fusion protein, thus preventing the foldback reaction and blocking the lipid mixing step of fusion. Our data reveal the existence of a relatively long-lived core trimer intermediate with which domain III interacts to initiate membrane fusion. These novel inhibitors of the class II fusion proteins show cross-inhibition within the virus genus and suggest that the domain III–core trimer interaction can serve as a new target for the development of antiviral reagents.

Structural comparison of three viral “fusion” proteins

1991 ◽  
Vol 19 (3) ◽  
pp. 312S-312S
Author(s):  
BRUCE H NICHOLSON ◽  
MAHMOUD NAASE
Keyword(s):  
Fusion Proteins ◽  
Viral Fusion ◽  
Structural Comparison ◽  
Viral Fusion Proteins

scholarly journals Dual Wavelength Imaging Allows Analysis of Membrane Fusion of Influenza Virus inside Cells

2006 ◽  
Vol 80 (4) ◽  
pp. 2013-2018 ◽  
Author(s):  
Tatsuya Sakai ◽  
Masanobu Ohuchi ◽  
Masaki Imai ◽  
Takafumi Mizuno ◽  
Kazunori Kawasaki ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Imaging Technique ◽  
Rapid Analysis ◽  
Virus Infectivity ◽  
Viral Fusion ◽  
The Novel ◽  
Influenza Virus Hemagglutinin ◽  
Highly Sensitive ◽  
Highly Sensitive Detection

ABSTRACT Influenza virus hemagglutinin (HA) is a determinant of virus infectivity. Therefore, it is important to determine whether HA of a new influenza virus, which can potentially cause pandemics, is functional against human cells. The novel imaging technique reported here allows rapid analysis of HA function by visualizing viral fusion inside cells. This imaging was designed to detect fusion changing the spectrum of the fluorescence-labeled virus. Using this imaging, we detected the fusion between a virus and a very small endosome that could not be detected previously, indicating that the imaging allows highly sensitive detection of viral fusion.

scholarly journals New Biophysical Approaches Reveal the Dynamics and Mechanics of Type I Viral Fusion Machinery and Their Interplay with Membranes

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 413 ◽  
Author(s):  
Mark A. Benhaim ◽  
Kelly K. Lee
Keyword(s):  
Membrane Fusion ◽  
Conformational Changes ◽  
Viral Entry ◽  
Fusion Proteins ◽  
Structural Changes ◽  
Fusion Reaction ◽  
Type I ◽  
Viral Fusion ◽  
Technological Advances ◽  
Viral Fusion Proteins

Protein-mediated membrane fusion is a highly regulated biological process essential for cellular and organismal functions and infection by enveloped viruses. During viral entry the membrane fusion reaction is catalyzed by specialized protein machinery on the viral surface. These viral fusion proteins undergo a series of dramatic structural changes during membrane fusion where they engage, remodel, and ultimately fuse with the host membrane. The structural and dynamic nature of these conformational changes and their impact on the membranes have long-eluded characterization. Recent advances in structural and biophysical methodologies have enabled researchers to directly observe viral fusion proteins as they carry out their functions during membrane fusion. Here we review the structure and function of type I viral fusion proteins and mechanisms of protein-mediated membrane fusion. We highlight how recent technological advances and new biophysical approaches are providing unprecedented new insight into the membrane fusion reaction.

Peptide models for the membrane destabilizing actions of viral fusion proteins

Biopolymers ◽  
1992 ◽  
Vol 32 (4) ◽  
pp. 309-314 ◽  
Author(s):  
Richard M. Epand ◽  
James J. Cheetham ◽  
Raquel F. Epand ◽  
Philip L. Yeagle ◽  
Christopher D. Richardson ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Viral Fusion ◽  
Peptide Models ◽  
Viral Fusion Proteins

Deacylation of influenza virus hemagglutinin does not affect the kinetics of low pH induced membrane fusion

1996 ◽  
Vol 431 (S6) ◽  
pp. R257-R258 ◽  
Author(s):  
Britta Schroth ◽  
Hans C. Philipp ◽  
Michael Veit ◽  
Michael F. G. Schmidt ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Low Ph ◽  
Induced Membrane ◽  
Influenza Virus Hemagglutinin ◽  
Kinetics Of
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